Skip to main content
SpringerLink
Log in

Pathological Diagnosis and Classification of Gastric Epithelial Tumours

  • Chapter
  • First Online:
Gastric Cancer In The Precision Medicine Era

Part of the book series: Current Clinical Pathology ((CCPATH))

Abstract

A correct diagnosis of benign gastric lesions, including intra-epithelial neoplasia/dysplasia and gastric epithelial polyps, may predict an incremental risk of progression of these lesions to gastric cancer. In this regard, almost all gastric carcinomas (95%) originate from glandular epithelium and are classified as adenocarcinomas. A multiplicity of environmental and genetic factors influences the aetiologies of this heterogeneous group of tumours, which are characterized by different morphologies, molecular backgrounds and histogenesis. Several systems have been proposed to classify gastric adenocarcinoma based on macroscopic and microscopic histological features, among which the two most commonly used are the Lauren and World Health Organization (WHO) systems. However, other uncommon histological variants do exist (5%) that are not an integral part of the conventional classification systems. Despite the ongoing decrease in morbidity and mortality, gastric cancer continues to be one of the leading types of fatal cancer worldwide, since the majority of patients in the West are diagnosed with advanced disease and only 6–10% of the cases is affected by early-stage cancer. In this regard, a substantial modification of tumour node metastasis (TNM) staging of gastric tumours has been operated in 2017. Although recent genetic and molecular advances lead to the association of hereditary predisposition and sporadic gastric carcinomas with several genes, opening a novel scenario into the identification of new potential therapeutic targets, an accurate and precise classification of gastric epithelial tumours represents the prerequisite to better understanding the biology of this tumoural entity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.

    CAS  PubMed  Google Scholar 

  2. Lauwers GY, Srivastava A. Gastric preneoplastic lesions and epithelial dysplasia. Gastroenterol Clin North Am. 2007;36(4):813–29, vi.

    Article  PubMed  Google Scholar 

  3. Lauwers GY, Carneiro F, Graham DY et al. Gastric carcinoma. In: Bosman FT, Carneiro F, Hruban RH. Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC; 2010. p. 48–58.

    Google Scholar 

  4. Rugge M, et al. Gastric dysplasia: the Padova international classification. Am J Surg Pathol. 2000;24(2):167–76.

    Article  CAS  PubMed  Google Scholar 

  5. Schlemper RJ, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47(2):251–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stolte M. The new Vienna classification of epithelial neoplasia of the gastrointestinal tract: advantages and disadvantages. Virchows Arch. 2003;442(2):99–106.

    PubMed  Google Scholar 

  7. Lansdown M, et al. High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma. Gut. 1990;31(9):977–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Di Gregorio C, et al. Gastric dysplasia. A follow-up study. Am J Gastroenterol. 1993;88(10):1714–9.

    PubMed  Google Scholar 

  9. Rugge M, et al. Gastric epithelial dysplasia: a prospective multicenter follow-up study from the Interdisciplinary Group on Gastric Epithelial Dysplasia. Hum Pathol. 1991;22(10):1002–8.

    Article  CAS  PubMed  Google Scholar 

  10. Saraga EP, Gardiol D, Costa J. Gastric dysplasia. A histological follow-up study. Am J Surg Pathol. 1987;11(10):788–96.

    Article  CAS  PubMed  Google Scholar 

  11. Fertitta AM, et al. Clinical significance of gastric dysplasia: a multicenter follow-up study. Gastrointestinal Endoscopic Pathology Study Group. Endoscopy. 1993;25(4):265–8.

    Article  CAS  PubMed  Google Scholar 

  12. Kokkola A, et al. Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study. J Clin Pathol. 1996;49(12):979–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yamada H, et al. Long-term follow-up study of gastric adenoma/dysplasia. Endoscopy. 2004;36(5):390–6.

    Article  CAS  PubMed  Google Scholar 

  14. Park DY, Lauwers GY. Gastric polyps: classification and management. Arch Pathol Lab Med. 2008;132(4):633–40.

    PubMed  Google Scholar 

  15. Carmack SW, et al. The current spectrum of gastric polyps: a 1-year national study of over 120,000 patients. Am J Gastroenterol. 2009;104(6):1524–32.

    Article  PubMed  Google Scholar 

  16. Genta RM, et al. No association between gastric fundic gland polyps and gastrointestinal neoplasia in a study of over 100,000 patients. Clin Gastroenterol Hepatol. 2009;7(8):849–54.

    Article  PubMed  Google Scholar 

  17. Fossmark R, et al. Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scand J Gastroenterol. 2008;43(1):20–4.

    Article  CAS  PubMed  Google Scholar 

  18. Ally MR, et al. Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps. Dig Dis Sci. 2009;54(12):2617–22.

    Article  CAS  PubMed  Google Scholar 

  19. Attard TM, et al. Fundic gland polyposis with high-grade dysplasia in a child with attenuated familial adenomatous polyposis and familial gastric cancer. J Pediatr Gastroenterol Nutr. 2001;32(2):215–8.

    Article  CAS  PubMed  Google Scholar 

  20. Abraham SC, et al. Sporadic fundic gland polyps with epithelial dysplasia : evidence for preferential targeting for mutations in the adenomatous polyposis coli gene. Am J Pathol. 2002;161(5):1735–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Worthley DL, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut. 2012;61(5):774–9.

    Article  CAS  PubMed  Google Scholar 

  22. Carmack SW, et al. Management of gastric polyps: a pathology-based guide for gastroenterologists. Nat Rev Gastroenterol Hepatol. 2009;6(6):331–41.

    Article  PubMed  Google Scholar 

  23. Canzonieri V, et al. Exocrine and endocrine modulation in common gastric carcinoma. Am J Clin Pathol. 2012;137(5):712–21.

    Article  PubMed  Google Scholar 

  24. Park DY, et al. Adenomatous and foveolar gastric dysplasia: distinct patterns of mucin expression and background intestinal metaplasia. Am J Surg Pathol. 2008;32(4):524–33.

    Article  PubMed  Google Scholar 

  25. Abraham SC, et al. Gastric adenomas: intestinal-type and gastric-type adenomas differ in the risk of adenocarcinoma and presence of background mucosal pathology. Am J Surg Pathol. 2002;26(10):1276–85.

    Article  PubMed  Google Scholar 

  26. Jass JR. A classification of gastric dysplasia. Histopathology. 1983;7(2):181–93.

    Article  CAS  PubMed  Google Scholar 

  27. Nogueira AM, et al. Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation. J Pathol. 1999;187(5):541–8.

    Article  CAS  PubMed  Google Scholar 

  28. Park DY, et al. CDX2 expression in the intestinal-type gastric epithelial neoplasia: frequency and significance. Mod Pathol. 2010;23(1):54–61.

    Article  CAS  PubMed  Google Scholar 

  29. Rubio CA. Paneth cell adenoma of the stomach. Am J Surg Pathol. 1989;13(4):325–8.

    Article  CAS  PubMed  Google Scholar 

  30. Lev R, DeNucci TD. Neoplastic Paneth cells in the stomach. Report of two cases and review of the literature. Arch Pathol Lab Med. 1989;113(2):129–33.

    CAS  PubMed  Google Scholar 

  31. Singhi AD, Lazenby AJ, Montgomery EA. Gastric adenocarcinoma with chief cell differentiation: a proposal for reclassification as oxyntic gland polyp/adenoma. Am J Surg Pathol. 2012;36(7):1030–5.

    Article  PubMed  Google Scholar 

  32. Torre LA, et al. Global cancer incidence and mortality rates and trends – an update. Cancer Epidemiol Biomarkers Prev. 2015;25(1):16–27.

    Article  PubMed  Google Scholar 

  33. Stock M, Otto F. Gene deregulation in gastric cancer. Gene. 2005;360(1):1–19.

    Article  CAS  PubMed  Google Scholar 

  34. Parkin DM, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  35. Curado MP, et al. Cancer incidence in five continents, vol. 9. Lyon: IARC Press International Agency for Research on Cancer; 2007.

    Google Scholar 

  36. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118(12):3030–44.

    Article  CAS  PubMed  Google Scholar 

  37. Munoz N, Franceschi S. Epidemiology of gastric cancer and perspectives for prevention. Salud Publica Mex. 1997;39(4):318–30.

    CAS  PubMed  Google Scholar 

  38. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process – First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52(24):6735–40.

    CAS  PubMed  Google Scholar 

  39. Yakirevich E, Resnick MB. Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin North Am. 2013;42(2):261–84.

    Article  PubMed  Google Scholar 

  40. Siurala M, Varis K, Wiljasalo M. Studies of patients with atrophic gastritis: a 10-15-year follow-up. Scand J Gastroenterol. 1966;1(1):40–8.

    Article  CAS  PubMed  Google Scholar 

  41. Walker IR, et al. Simple atrophic gastritis and gastric carcinoma. Gut. 1971;12(11):906–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dixon MF, et al. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161–81.

    Article  CAS  PubMed  Google Scholar 

  43. Rugge M, Genta RM. Staging and grading of chronic gastritis. Hum Pathol. 2005;36(3):228–33.

    Article  PubMed  Google Scholar 

  44. Rugge M, et al. Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study. Aliment Pharmacol Ther. 2010;31(10):1104–11.

    CAS  PubMed  Google Scholar 

  45. Jass JR, Filipe MI. The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants and gastric carcinoma. Histochem J. 1981;13(6):931–9.

    Article  CAS  PubMed  Google Scholar 

  46. Reis CA, et al. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res. 1999;59(5):1003–7.

    CAS  PubMed  Google Scholar 

  47. Filipe MI, et al. Incomplete sulphomucin-secreting intestinal metaplasia for gastric cancer. Preliminary data from a prospective study from three centres. Gut. 1985;26(12):1319–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jass JR, Filipe MI. Sulphomucins and precancerous lesions of the human stomach. Histopathology. 1980;4(3):271–9.

    Article  CAS  PubMed  Google Scholar 

  49. Barros R, et al. Gastric intestinal metaplasia revisited: function and regulation of CDX2. Trends Mol Med. 2012;18(9):555–63.

    Article  CAS  PubMed  Google Scholar 

  50. Pagnini CA, Bozzola L. Precancerous significance of colonic type intestinal metaplasia. Tumori. 1981;67(2):113–6.

    Article  CAS  PubMed  Google Scholar 

  51. Filipe MI, et al. Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 1994;57(3):324–9.

    Article  CAS  PubMed  Google Scholar 

  52. Capelle LG, et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71(7):1150–8.

    Article  PubMed  Google Scholar 

  53. Correa P, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000;92(23):1881–8.

    Article  CAS  PubMed  Google Scholar 

  54. Ley C, et al. Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13(1):4–10.

    Article  CAS  PubMed  Google Scholar 

  55. Zhou L, et al. A five-year follow-up study on the pathological changes of gastric mucosa after H. pylori eradication. Chin Med J (Engl). 2003;116(1):11–4.

    Article  Google Scholar 

  56. Wong BC, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291(2):187–94.

    Article  CAS  PubMed  Google Scholar 

  57. Asfeldt AM, et al. The natural course of Helicobacter pylori infection on endoscopic findings in a population during 17 years of follow-up: the Sorreisa gastrointestinal disorder study. Eur J Epidemiol. 2009;24(10):649–58.

    Article  PubMed  Google Scholar 

  58. Barros R, et al. Relevance of high virulence Helicobacter pylori strains and futility of CDX2 expression for predicting intestinal metaplasia after eradication of infection. Scand J Gastroenterol. 2010;45(7-8):828–34.

    Article  PubMed  Google Scholar 

  59. Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut. 1999;44(6):890–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Schmidt PH, et al. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest. 1999;79(6):639–46.

    CAS  PubMed  Google Scholar 

  61. Halldorsdottir AM, et al. Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland. Dig Dis Sci. 2003;48(3):431–41.

    Article  CAS  PubMed  Google Scholar 

  62. Yamaguchi H, et al. Identification of spasmolytic polypeptide expressing metaplasia (SPEM) in remnant gastric cancer and surveillance postgastrectomy biopsies. Dig Dis Sci. 2002;47(3):573–8.

    Article  PubMed  Google Scholar 

  63. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241.

    Google Scholar 

  64. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest. 2007;117(1):60–9.

    Article  CAS  PubMed  Google Scholar 

  65. Uemura N, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345(11):784–9.

    Article  CAS  PubMed  Google Scholar 

  66. Malfertheiner P, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56(6):772–81.

    Article  CAS  PubMed  Google Scholar 

  67. Ekstrom AM, et al. Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: a population-based case-control study in Sweden. Int J Cancer. 2000;87(1):133–40.

    Article  CAS  PubMed  Google Scholar 

  68. Epplein M, et al. Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii. Cancer Causes Control. 2008;19(8):869–77.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Kono S, Hirohata T. Nutrition and stomach cancer. Cancer Causes Control. 1996;7(1):41–55.

    Article  CAS  PubMed  Google Scholar 

  70. Buckland G, et al. Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study. Int J Cancer. 2015;137(3):598–606.

    Article  CAS  PubMed  Google Scholar 

  71. Lin SH, et al. Salt processed food and gastric cancer in a Chinese population. Asian Pac J Cancer Prev. 2014;15(13):5293–8.

    Article  PubMed  Google Scholar 

  72. Massarrat S, Stolte M. Development of gastric cancer and its prevention. Arch Iran Med. 2014;17(7):514–20.

    PubMed  Google Scholar 

  73. Nomura AM, et al. Case-control study of diet and other risk factors for gastric cancer in Hawaii (United States). Cancer Causes Control. 2003;14(6):547–58.

    Article  PubMed  Google Scholar 

  74. Bjelakovic G, et al. Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther. 2008;28(6):689–703.

    Article  CAS  PubMed  Google Scholar 

  75. Qiao YL, et al. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst. 2009;101(7):507–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jenab M, et al. Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition. Br J Cancer. 2006;95(3):406–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ladeiras-Lopes R, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2008;19(7):689–701.

    Article  PubMed  Google Scholar 

  78. Nishino Y, et al. Tobacco smoking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2006;36(12):800–7.

    Article  PubMed  Google Scholar 

  79. Thorban S, et al. Prognostic factors in gastric stump carcinoma. Ann Surg. 2000;231(2):188–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Skierucha M, et al. Molecular alterations in gastric cancer with special reference to the early-onset subtype. World J Gastroenterol. 2016;22(8):2460–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sons HU, Borchard F. Gastric carcinoma after surgical treatment for benign ulcer disease: some pathologic-anatomic aspects. Int Surg. 1987;72(4):222–6.

    CAS  PubMed  Google Scholar 

  82. Sinning C, et al. Gastric stump carcinoma – epidemiology and current concepts in pathogenesis and treatment. Eur J Surg Oncol. 2007;33(2):133–9.

    Article  CAS  PubMed  Google Scholar 

  83. Offerhaus GJ, et al. Mortality caused by stomach cancer after remote partial gastrectomy for benign conditions: 40 years of follow up of an Amsterdam cohort of 2633 postgastrectomy patients. Gut. 1988;29(11):1588–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Toftgaard C. Gastric cancer after peptic ulcer surgery. A historic prospective cohort investigation. Ann Surg. 1989;210(2):159–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tersmette AC, et al. Multivariate analysis of the risk of stomach cancer after ulcer surgery in an Amsterdam cohort of postgastrectomy patients. Am J Epidemiol. 1991;134(1):14–21.

    Article  CAS  PubMed  Google Scholar 

  86. Imai S, et al. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci U S A. 1994;91(19):9131–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yamamoto N, et al. Epstein-Barr virus and gastric remnant cancer. Cancer. 1994;74(3):805–9.

    Article  CAS  PubMed  Google Scholar 

  88. van Rees BP, et al. Different pattern of allelic loss in Epstein-Barr virus-positive gastric cancer with emphasis on the p53 tumor suppressor pathway. Am J Pathol. 2002;161(4):1207–13.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Baas IO, et al. Helicobacter pylori and Epstein-Barr virus infection and the p53 tumour suppressor pathway in gastric stump cancer compared with carcinoma in the non-operated stomach. J Clin Pathol. 1998;51(9):662–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Offerhaus GJ, et al. The mucosa of the gastric remnant harboring malignancy. Histologic findings in the biopsy specimens of 504 asymptomatic patients 15 to 46 years after partial gastrectomy with emphasis on nonmalignant lesions. Cancer. 1989;64(3):698–703.

    Article  CAS  PubMed  Google Scholar 

  91. Borrmann R. Geshwulste des Magens und Duodenums. In: Henke F, Lubrasch O, editors. Handbuch der Speziellen Pathologischen Anatomie und Histologie. Berlin: Springer; 1926.

    Google Scholar 

  92. Ming SC. Gastric carcinoma. A pathobiological classification. Cancer. 1977;39(6):2475–85.

    Article  CAS  PubMed  Google Scholar 

  93. Carneiro F, Ribeiro MM, Sobrinho-Simoes M. Prognostic factors in gastric carcinoma. Br J Cancer. 1997;76(2):278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Goseki N, Takizawa T, Koike M. Differences in the mode of the extension of gastric cancer classified by histological type: new histological classification of gastric carcinoma. Gut. 1992;33(5):606–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.

    Article  CAS  PubMed  Google Scholar 

  96. Tay ST, et al. A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes. Cancer Res. 2003;63(12):3309–16.

    CAS  PubMed  Google Scholar 

  97. Tan IB, et al. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology. 2011;141(2):476–85.

    Article  PubMed  Google Scholar 

  98. Lee HS, et al. Protein expression profiling and molecular classification of gastric cancer by the tissue array method. Clin Cancer Res. 2007;13(14):4154–63.

    Article  CAS  PubMed  Google Scholar 

  99. Brierley JD, Gospodarowicz MK, Wittekind C, editors. TNM classification of malignant tumours. 8th ed. Chichester: Wiley-Blackwell; 2017.

    Google Scholar 

  100. Amin MB, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer International Publishing; 2017.

    Google Scholar 

  101. Eom DW, et al. Gastric micropapillary carcinoma: a distinct subtype with a significantly worse prognosis in TNM stages I and II. Am J Surg Pathol. 2010;35(1):84–91.

    Article  Google Scholar 

  102. Carvalho B, et al. Mixed gastric carcinomas show similar chromosomal aberrations in both their diffuse and glandular components. Cell Oncol. 2006;28(5-6):283–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zheng HC, et al. Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch. 2008;452(5):525–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Machado JC, et al. E-cadherin gene mutations provide a genetic basis for the phenotypic divergence of mixed gastric carcinomas. Lab Invest. 1999;79(4):459–65.

    CAS  PubMed  Google Scholar 

  105. Park SY, et al. Mixed-type gastric cancer and its association with high-frequency CpG island hypermethylation. Virchows Arch. 2010;456(6):625–33.

    Article  CAS  PubMed  Google Scholar 

  106. Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995;333(1):32–41.

    Article  CAS  PubMed  Google Scholar 

  107. Berlth F, et al. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol. 2014;20(19):5679–84.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Cislo M, et al. Distinct molecular subtypes of gastric cancer: from Lauren to molecular pathology. Oncotarget. 2018;9(27):19427–42.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Van Cutsem E, et al. Gastric cancer. Lancet. 2016;388(10060):2654–64.

    Article  PubMed  CAS  Google Scholar 

  110. Martin IG, et al. Goseki histological grading of gastric cancer is an important predictor of outcome. Gut. 1994;35(6):758–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Carneiro F. Classification of gastric carcinomas. Curr Diagn Pathol. 1997;4(1):51–59.

    Article  Google Scholar 

  112. Carneiro F, Seixas M, Sobrinho-Simoes M. New elements for an updated classification of the carcinomas of the stomach. Pathol Res Pract. 1995;191(6):571–84.

    Article  CAS  PubMed  Google Scholar 

  113. Machado JC, et al. pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study. Eur J Cancer. 1996;32A(9):1585–90.

    Article  CAS  PubMed  Google Scholar 

  114. Machado JC, et al. Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). J Pathol. 2000;190(4):437–43.

    Article  CAS  PubMed  Google Scholar 

  115. Kushima R, et al. Gastric-type well-differentiated adenocarcinoma and pyloric gland adenoma of the stomach. Gastric Cancer. 2006;9(3):177–84.

    Article  PubMed  Google Scholar 

  116. Kushima R, Hattori T. Histogenesis and characteristics of gastric-type adenocarcinomas in the stomach. J Cancer Res Clin Oncol. 1993;120(1-2):103–11.

    Article  CAS  PubMed  Google Scholar 

  117. Tsukashita S, et al. MUC gene expression and histogenesis of adenocarcinoma of the stomach. Int J Cancer. 2001;94(2):166–70.

    Article  CAS  PubMed  Google Scholar 

  118. Shiroshita H, et al. Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains. Pathol Int. 2004;54(5):311–21.

    Article  CAS  PubMed  Google Scholar 

  119. Tatematsu M, Tsukamoto T, Mizoshita T. Role of Helicobacter pylori in gastric carcinogenesis: the origin of gastric cancers and heterotopic proliferative glands in Mongolian gerbils. Helicobacter. 2005;10(2):97–106.

    Article  PubMed  Google Scholar 

  120. Blumenfeld W, et al. Neuroendocrine differentiation in gastric adenocarcinomas. An immunohistochemical study. Arch Pathol Lab Med. 1996;120(5):478–81.

    CAS  PubMed  Google Scholar 

  121. Park JG, et al. Chromogranin-A expression in gastric and colon cancer tissues. Int J Cancer. 1992;51(2):189–94.

    Article  CAS  PubMed  Google Scholar 

  122. Sentani K, et al. Immunostaining of gastric cancer with neuroendocrine differentiation: Reg IV-positive neuroendocrine cells are associated with gastrin, serotonin, pancreatic polypeptide and somatostatin. Pathol Int. 2010;60(4):291–7.

    Article  PubMed  Google Scholar 

  123. Waldum HL, et al. Neuroendocrine differentiation in human gastric carcinoma. Cancer. 1998;83(3):435–44.

    Article  CAS  PubMed  Google Scholar 

  124. Yao GY, et al. Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases. World J Gastroenterol. 2003;9(4):858–61.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Jiang SX, et al. Gastric large cell neuroendocrine carcinomas: a distinct clinicopathologic entity. Am J Surg Pathol. 2006;30(8):945–53.

    Article  PubMed  Google Scholar 

  126. Mori M, Iwashita A, Enjoji M. Adenosquamous carcinoma of the stomach. A clinicopathologic analysis of 28 cases. Cancer. 1986;57(2):333–9.

    Article  CAS  PubMed  Google Scholar 

  127. Mori M, Fukuda T, Enjoji M. Adenosquamous carcinoma of the stomach. Histogenetic and ultrastructural studies. Gastroenterology. 1987;92(4):1078–82.

    Article  CAS  PubMed  Google Scholar 

  128. Boswell JT, Helwig EB. Squamous Cell Carcinoma and Adenoacanthoma of the Stomach. A Clinicopathologic Study. Cancer. 1965;18:181–92.

    Article  CAS  PubMed  Google Scholar 

  129. Bonnheim DC, Sarac OK, Fett W. Primary squamous cell carcinoma of the stomach. Am J Gastroenterol. 1985;80(2):91–4.

    CAS  PubMed  Google Scholar 

  130. Marubashi S, et al. Primary squamous cell carcinoma of the stomach. Gastric Cancer. 1999;2(2):136–41.

    Article  PubMed  Google Scholar 

  131. Yoshida K, et al. Early gastric cancer of adenosquamous carcinoma type: report of a case and review of literature. Jpn J Clin Oncol. 1996;26(4):252–7.

    Article  CAS  PubMed  Google Scholar 

  132. Ishikura H, et al. Hepatoid adenocarcinomas of the stomach. An analysis of seven cases. Cancer. 1986;58(1):119–26.

    Article  CAS  PubMed  Google Scholar 

  133. Nagai E, et al. Hepatoid adenocarcinoma of the stomach. A clinicopathologic and immunohistochemical analysis. Cancer. 1993;72(6):1827–35.

    Article  CAS  PubMed  Google Scholar 

  134. Chang YC, et al. Clinicopathologic features and long-term results of alpha-fetoprotein-producing gastric cancer. Am J Gastroenterol. 1990;85(11):1480–5.

    CAS  PubMed  Google Scholar 

  135. Akiyama S, et al. Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma. Int J Cancer. 2003;106(4):510–5.

    Article  CAS  PubMed  Google Scholar 

  136. Petrella T, et al. Alphafetoprotein-producing gastric adenocarcinoma. Histopathology. 1995;26(2):171–5.

    Article  CAS  PubMed  Google Scholar 

  137. Kumashiro Y, et al. Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. Hum Pathol. 2007;38(6):857–63.

    Article  CAS  PubMed  Google Scholar 

  138. Ishikura H, et al. Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases. Histopathology. 1997;31(1):47–54.

    Article  CAS  PubMed  Google Scholar 

  139. Liu X, et al. Analysis of clinicopathologic features and prognostic factors in hepatoid adenocarcinoma of the stomach. Am J Surg Pathol. 2010;34(10):1465–71.

    Article  PubMed  Google Scholar 

  140. Motoyama T, et al. alpha-Fetoprotein producing gastric carcinomas: a comparative study of three different subtypes. Acta Pathol Jpn. 1993;43(11):654–61.

    CAS  PubMed  Google Scholar 

  141. Inagawa S, et al. Hepatoid adenocarcinoma of the stomach. Gastric Cancer. 2001;4(1):43–52.

    Article  CAS  PubMed  Google Scholar 

  142. Supriatna Y, et al. Evidence for hepatocellular differentiation in alpha-fetoprotein-negative gastric adenocarcinoma with hepatoid morphology: a study with in situ hybridisation for albumin mRNA. Pathology. 2005;37(3):211–5.

    Article  CAS  PubMed  Google Scholar 

  143. Sentani K, et al. Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach. Mod Pathol. 2008;21(4):464–75.

    Article  CAS  PubMed  Google Scholar 

  144. Terracciano LM, et al. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. Am J Surg Pathol. 2003;27(10):1302–12.

    Article  PubMed  Google Scholar 

  145. Saigo PE, et al. Primary gastric choriocarcinoma. An immunohistological study. Am J Surg Pathol. 1981;5(4):333–42.

    Article  CAS  PubMed  Google Scholar 

  146. Liu AY, et al. Gastric choriocarcinoma shows characteristics of adenocarcinoma and gestational choriocarcinoma: a comparative genomic hybridization and fluorescence in situ hybridization study. Diagn Mol Pathol. 2001;10(3):161–5.

    Article  CAS  PubMed  Google Scholar 

  147. Smith FR, Barkin JS, Hensley G. Choriocarcinoma of the stomach. Am J Gastroenterol. 1980;73(1):45–8.

    CAS  PubMed  Google Scholar 

  148. Yonezawa S, et al. Immunohistochemical localization of thrombomodulin in chorionic diseases of the uterus and choriocarcinoma of the stomach. A comparative study with the distribution of human chorionic gonadotropin. Cancer. 1988;62(3):569–76.

    Article  CAS  PubMed  Google Scholar 

  149. Krulewski T, Cohen LB. Choriocarcinoma of the stomach: pathogenesis and clinical characteristics. Am J Gastroenterol. 1988;83(10):1172–5.

    CAS  PubMed  Google Scholar 

  150. Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004;4(10):757–68.

    Article  CAS  PubMed  Google Scholar 

  151. Murphy G, et al. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009;137(3):824–33.

    Article  PubMed  Google Scholar 

  152. Lee JH, et al. Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2009;24(3):354–65.

    Article  PubMed  Google Scholar 

  153. Willems S, Carneiro F, Geboes K. Gastric carcinoma with osteoclast-like giant cells and lymphoepithelioma-like carcinoma of the stomach: two of a kind? Histopathology. 2005;47(3):331–3.

    Article  CAS  PubMed  Google Scholar 

  154. Minamoto T, et al. Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor. Cancer. 1990;66(5):945–52.

    Article  CAS  PubMed  Google Scholar 

  155. Watanabe H, Enjoji M, Imai T. Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations. Cancer. 1976;38(1):232–43.

    Article  CAS  PubMed  Google Scholar 

  156. Wang HH, et al. Lymphoepithelioma-like carcinoma of the stomach: a subset of gastric carcinoma with distinct clinicopathological features and high prevalence of Epstein-Barr virus infection. Hepatogastroenterology. 1999;46(26):1214–9.

    CAS  PubMed  Google Scholar 

  157. Matsunou H, et al. Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan. Cancer. 1996;77(10):1998–2004.

    Article  CAS  PubMed  Google Scholar 

  158. Truong CD, et al. Characteristics of Epstein-Barr virus-associated gastric cancer: a study of 235 cases at a comprehensive cancer center in U.S.A. J Exp Clin Cancer Res. 2009;28:14.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Fukayama M, Chong JM, Kaizaki Y. Epstein-Barr virus and gastric carcinoma. Gastric Cancer. 1998;1(2):104–14.

    Article  PubMed  Google Scholar 

  160. Cho KJ, et al. Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study. APMIS. 1990;98(11):991–5.

    Article  CAS  PubMed  Google Scholar 

  161. Nakayama Y, et al. Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation. Pathol Int. 1997;47(8):557–63.

    Article  CAS  PubMed  Google Scholar 

  162. Sato Y, et al. Gastric carcinosarcoma, coexistence of adenosquamous carcinoma and rhabdomyosarcoma: a case report. Histopathology. 2001;39(5):543–4.

    Article  CAS  PubMed  Google Scholar 

  163. Randjelovic T, et al. Carcinosarcoma of the stomach: a case report and review of the literature. World J Gastroenterol. 2007;13(41):5533–6.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Tsuneyama K, et al. A case report of gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation. Pathol Res Pract. 1999;195(2):93–7; discussion 98.

    Article  CAS  PubMed  Google Scholar 

  165. Yamazaki K. A gastric carcinosarcoma with neuroendocrine cell differentiation and undifferentiated spindle-shaped sarcoma component possibly progressing from the conventional tubular adenocarcinoma; an immunohistochemical and ultrastructural study. Virchows Arch. 2003;442(1):77–81.

    PubMed  Google Scholar 

  166. Teramachi K, et al. Carcinosarcoma (pure endocrine cell carcinoma with sarcoma components) of the stomach. Pathol Int. 2003;53(8):552–6.

    Article  PubMed  Google Scholar 

  167. Kuroda N, et al. Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma component and leiomyosarcomatous and myofibroblastic differentiation as the sarcomatous component. APMIS. 2006;114(3):234–8.

    Article  CAS  PubMed  Google Scholar 

  168. Ikeda Y, et al. Gastric carcinosarcoma presenting as a huge epigastric mass. Gastric Cancer. 2007;10(1):63–8.

    Article  PubMed  Google Scholar 

  169. Roh JH, et al. Micropapillary carcinoma of stomach: a clinicopathologic and immunohistochemical study of 11 cases. Am J Surg Pathol. 2010;34(8):1139–46.

    Article  PubMed  Google Scholar 

  170. Capella C, et al. Gastric parietal cell carcinoma – a newly recognized entity: light microscopic and ultrastructural features. Histopathology. 1984;8(5):813–24.

    Article  CAS  PubMed  Google Scholar 

  171. Byrne D, Holley MP, Cuschieri A. Parietal cell carcinoma of the stomach: association with long-term survival after curative resection. Br J Cancer. 1988;58(1):85–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Yang GY, et al. Parietal cell carcinoma of gastric cardia: immunophenotype and ultrastructure. Ultrastruct Pathol. 2003;27(2):87–94.

    Article  PubMed  Google Scholar 

  173. Hayashi I, et al. Mucoepidermoid carcinoma of the stomach. J Surg Oncol. 1987;34(2):94–9.

    Article  CAS  PubMed  Google Scholar 

  174. Kazzaz BA, Eulderink F. Paneth cell-rich carcinoma of the stomach. Histopathology. 1989;15(3):303–5.

    Article  CAS  PubMed  Google Scholar 

  175. Ooi A, et al. Predominant Paneth cell differentiation in an intestinal type gastric cancer. Pathol Res Pract. 1991;187(2-3):220–5.

    Article  CAS  PubMed  Google Scholar 

  176. Caruso RA, Famulari C. Neoplastic Paneth cells in adenocarcinoma of the stomach: a case report. Hepatogastroenterology. 1992;39(3):264–6.

    CAS  PubMed  Google Scholar 

  177. Ueyama T, et al. Vimentin-positive gastric carcinomas with rhabdoid features. A clinicopathologic and immunohistochemical study. Am J Surg Pathol. 1993;17(8):813–9.

    Article  CAS  PubMed  Google Scholar 

  178. Pinto JA, et al. Well differentiated gastric adenocarcinoma with rhabdoid areas: a case report with immunohistochemical analysis. Pathol Res Pract. 1997;193(11-12):801–5; discussion 806–8.

    Article  CAS  PubMed  Google Scholar 

  179. Rivera-Hueto F, et al. Early gastric stump carcinoma with rhabdoid features. Case report. Pathol Res Pract. 1999;195(12):841–6.

    Article  CAS  PubMed  Google Scholar 

  180. Murakami T. Pathomorphological diagnosis. In: Murakami T, editor. Early gastric cancer. Tokyo: University of Tokyo; 1971.

    Google Scholar 

  181. Tsukuma H, Mishima T, Oshima A. Prospective study of “early” gastric cancer. Int J Cancer. 1983;31(4):421–6.

    Article  CAS  PubMed  Google Scholar 

  182. Everett SM, Axon AT. Early gastric cancer in Europe. Gut. 1997;41(2):142–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Noguchi Y, et al. Is gastric carcinoma different between Japan and the United States? Cancer. 2000;89(11):2237–46.

    Article  CAS  PubMed  Google Scholar 

  184. Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer. 2007;10(1):1–11.

    Article  PubMed  Google Scholar 

  185. Ming SC. Malignant epithelial tumours of the stomach. In: Ming SC, Goldman H, editors. Pathology of gastointestinal tract. Baltimore: Williams & Wilkins; 1998.

    Google Scholar 

  186. Oohara T, et al. Minute gastric cancers less than 5 mm in diameter. Cancer. 1982;50(4):801–10.

    Article  CAS  PubMed  Google Scholar 

  187. Kodama Y, et al. Growth patterns and prognosis in early gastric carcinoma. Superficially spreading and penetrating growth types. Cancer. 1983;51(2):320–6.

    Article  CAS  PubMed  Google Scholar 

  188. Xuan ZX, et al. Time trends of early gastric carcinoma. A clinicopathologic analysis of 2846 cases. Cancer. 1993;72(10):2889–94.

    Article  CAS  PubMed  Google Scholar 

  189. Zinninger MM, Collins WT. Extension of garcinoma of the stomach into the duodenum and esophagus. Ann Surg. 1949;130(3):557–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Fernet P, Azar HA, Stout AP. Intramural (tubal) spread of linitis plastica along the alimentary tract. Gastroenterology. 1965;48:419–24.

    Article  CAS  PubMed  Google Scholar 

  191. Maruyama K, et al. Lymph node metastases of gastric cancer. General pattern in 1931 patients. Ann Surg. 1989;210(5):596–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Duarte I, Llanos O. Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach. Hum Pathol. 1981;12(3):237–42.

    Article  CAS  PubMed  Google Scholar 

  193. Marano L, et al. Surgical management of advanced gastric cancer: An evolving issue. Eur J Surg Oncol. 2016;42(1):18–27.

    Article  CAS  PubMed  Google Scholar 

  194. Ishigami S, et al. Clinical merit of subdividing gastric cancer according to invasion of the muscularis propria. Hepatogastroenterology. 2004;51(57):869–71.

    PubMed  Google Scholar 

  195. Yoshikawa K, Maruyama K. Characteristics of gastric cancer invading to the proper muscle layer – with special reference to mortality and cause of death. Jpn J Clin Oncol. 1985;15(3):499–503.

    CAS  PubMed  Google Scholar 

  196. Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer. 2000;88(4):921–32.

    Article  CAS  PubMed  Google Scholar 

  197. Reid-Lombardo KM, et al. Treatment of gastric adenocarcinoma may differ among hospital types in the United States, a report from theNational Cancer Data Base. J Gastrointest Surg. 2007;11(4):410–9; discussion 419–20

    Article  PubMed  PubMed Central  Google Scholar 

  198. Siewert JR, et al. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228(4):449–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Wanebo HJ, et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993;218(5):583–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Karpeh MS, et al. Lymph node staging in gastric cancer: is location more important than Number? An analysis of 1,038 patients. Ann Surg. 2000;232(3):362–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Landry J, et al. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990;19(6):1357–62.

    Article  CAS  PubMed  Google Scholar 

  202. Carneiro F. Hereditary gastric cancer. Pathologe. 2012;33 Suppl 2(2012):231–4.

    Article  CAS  PubMed  Google Scholar 

  203. Vasen HF, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol. 2001;19(20):4074–80.

    Article  CAS  PubMed  Google Scholar 

  204. Capelle LG, et al. Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands. Gastroenterology. 2010;138(2):487–92.

    Article  PubMed  Google Scholar 

  205. Lynch HT, et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Jagelman DG, DeCosse JJ, Bussey HJ. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet. 1988;1(8595):1149–51.

    Article  CAS  PubMed  Google Scholar 

  207. Aarnio M, et al. Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer. 1997;74(5):551–5.

    Article  CAS  PubMed  Google Scholar 

  208. Varley JM, et al. An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. J Med Genet. 1995;32(12):942–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Shinmura K, et al. A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer. Clin Genet. 2005;67(1):81–6.

    Article  CAS  PubMed  Google Scholar 

  210. Takahashi M, et al. A novel germline mutation of the LKB1 gene in a patient with Peutz-Jeghers syndrome with early-onset gastric cancer. J Gastroenterol. 2004;39(12):1210–4.

    Article  PubMed  Google Scholar 

  211. Guilford P, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392(6674):402–5.

    Article  CAS  PubMed  Google Scholar 

  212. Caldas C, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36(12):873–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  213. Keller G, et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol. 1999;155(2):337–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Brooks-Wilson AR, et al. Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet. 2004;41(7):508–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Suriano G, et al. Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin Cancer Res. 2005;11(15):5401–9.

    Article  CAS  PubMed  Google Scholar 

  216. Kaurah P, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007;297(21):2360–72.

    Article  CAS  PubMed  Google Scholar 

  217. Schrader KA, et al. Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam Cancer. 2008;7(1):73–82.

    Article  PubMed  Google Scholar 

  218. Guilford PJ, et al. E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat. 1999;14(3):249–55.

    Article  CAS  PubMed  Google Scholar 

  219. Oliveira C, Seruca R, Carneiro F. Hereditary gastric cancer. Best Pract Res Clin Gastroenterol. 2009;23(2):147–57.

    Article  CAS  PubMed  Google Scholar 

  220. Oliveira C, et al. Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet. 2009;18(9):1545–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Blair V, et al. Hereditary diffuse gastric cancer: diagnosis and management. Clin Gastroenterol Hepatol. 2006;4(3):262–75.

    Article  CAS  PubMed  Google Scholar 

  222. Carneiro F, et al. Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer. J Clin Pathol. 2008;61(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  223. Grady WM, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26(1):16–7.

    Article  CAS  PubMed  Google Scholar 

  224. Oliveira C, et al. Quantification of epigenetic and genetic 2nd hits in CDH1 during hereditary diffuse gastric cancer syndrome progression. Gastroenterology. 2009;136(7):2137–48.

    Article  CAS  PubMed  Google Scholar 

  225. Barber M, et al. Mechanisms and sequelae of E-cadherin silencing in hereditary diffuse gastric cancer. J Pathol. 2008;216(3):295–306.

    Article  CAS  PubMed  Google Scholar 

  226. Guo J, et al. Genomic landscape of gastric cancer: molecular classification and potential targets. Sci China Life Sci. 2017;60(2):126–37.

    Article  CAS  PubMed  Google Scholar 

  227. Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ. 2004;157:327–49.

    Google Scholar 

  228. Kawauchi S, et al. Genomic instability and DNA ploidy are linked to DNA copy number aberrations of 8p23 and 22q11.23 in gastric cancers. Int J Mol Med. 2010;26(3):333–9.

    PubMed  Google Scholar 

  229. Aguilera A, Gomez-Gonzalez B. Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet. 2008;9(3):204–17.

    Article  CAS  PubMed  Google Scholar 

  230. Terada T. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: II. Expression of MUC1, MUC2, MUC5AC, and MUC6 in normal mucosa and in 42 cases. Int J Clin Exp Pathol. 2013;6(4):613–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  231. Yoda Y, et al. Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer. Gastric Cancer. 2015;18(1):65–76.

    Article  CAS  PubMed  Google Scholar 

  232. Toyota M, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59(21):5438–42.

    CAS  PubMed  Google Scholar 

  233. Enomoto S, et al. Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae. Cancer Sci. 2007;98(12):1853–61.

    Article  CAS  PubMed  Google Scholar 

  234. Fu DG. Epigenetic alterations in gastric cancer (Review). Mol Med Rep. 2015;12(3):3223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Kang GH, et al. Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. Lab Invest. 2003;83(5):635–41.

    Article  CAS  PubMed  Google Scholar 

  236. Kang GH, et al. DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest. 2008;88(2):161–70.

    Article  CAS  PubMed  Google Scholar 

  237. Park SY, et al. CpG island hypermethylator phenotype in gastric carcinoma and its clinicopathological features. Virchows Arch. 2010;457(4):415–22.

    Article  CAS  PubMed  Google Scholar 

  238. Becker KF, et al. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994;54(14):3845–52.

    CAS  PubMed  Google Scholar 

  239. Jawhari A, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival. Gastroenterology. 1997;112(1):46–54.

    Article  CAS  PubMed  Google Scholar 

  240. Ascano JJ, et al. Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer. Mod Pathol. 2001;14(10):942–9.

    Article  CAS  PubMed  Google Scholar 

  241. Machado JC, et al. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene. 2001;20(12):1525–8.

    Article  CAS  PubMed  Google Scholar 

  242. Chan AO. E-cadherin in gastric cancer. World J Gastroenterol. 2006;12(2):199–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Feakins RM, et al. Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival. Hum Pathol. 2003;34(12):1276–82.

    Article  CAS  PubMed  Google Scholar 

  244. Nakatsuru S, et al. Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma. Hum Mol Genet. 1992;1(8):559–63.

    Article  CAS  PubMed  Google Scholar 

  245. Tamura G, et al. Mutations of the APC gene occur during early stages of gastric adenoma development. Cancer Res. 1994;54(5):1149–51.

    CAS  PubMed  Google Scholar 

  246. Seruca R, et al. p53 alterations in gastric carcinoma: a study of 56 primary tumors and 204 nodal metastases. Cancer Genet Cytogenet. 1994;75(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  247. Lee JH, et al. Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma. Am J Pathol. 2002;161(2):611–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Nishizuka S, et al. Loss of heterozygosity during the development and progression of differentiated adenocarcinoma of the stomach. J Pathol. 1998;185(1):38–43.

    Article  CAS  PubMed  Google Scholar 

  249. Uchino S, et al. Frequent loss of heterozygosity at the DCC locus in gastric cancer. Cancer Res. 1992;52(11):3099–102.

    CAS  PubMed  Google Scholar 

  250. Li YL, et al. Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. World J Gastroenterol. 2005;11(2):285–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Kakeji Y, et al. Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. Br J Cancer. 1993;67(3):589–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Yonemura Y, et al. Correlation of p53 expression and proliferative activity in gastric cancer. Anal Cell Pathol. 1993;5(5):277–88.

    CAS  PubMed  Google Scholar 

  253. Ikeguchi M, et al. Mutated p53 protein expression and proliferative activity in advanced gastric cancer. Hepatogastroenterology. 1999;46(28):2648–53.

    CAS  PubMed  Google Scholar 

  254. Oda N, et al. DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;58(4):273–7.

    CAS  PubMed  Google Scholar 

  255. Varis A, et al. Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer. 2004;109(4):548–53.

    Article  CAS  PubMed  Google Scholar 

  256. Barros-Silva JD, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 2009;100(3):487–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Brennetot C, et al. Frequent Ki-ras mutations in gastric tumors of the MSI phenotype. Gastroenterology. 2003;125(4):1282.

    Article  PubMed  Google Scholar 

  258. Kim IJ, et al. Mutational analysis of BRAF and K-ras in gastric cancers: absence of BRAF mutations in gastric cancers. Hum Genet. 2003;114(1):118–20.

    Article  CAS  PubMed  Google Scholar 

  259. Oliveira C, et al. BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene. 2003;22(57):9192–6.

    Article  CAS  PubMed  Google Scholar 

  260. Wu M, et al. BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer. 2004;7(4):246–53.

    Article  CAS  PubMed  Google Scholar 

  261. Fassan M, et al. Early HER2 dysregulation in gastric and oesophageal carcinogenesis. Histopathology. 2012;61(5):769–76.

    Article  PubMed  Google Scholar 

  262. Bang YJ, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.

    Article  CAS  PubMed  Google Scholar 

  263. Ruschoff J, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457(3):299–307.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  264. Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2010;18(1):53–9.

    Article  CAS  Google Scholar 

  265. Available at: www.ema.europa.eu/pdfs/human/opinion/Herceptin_82246709en.pdf. (Accessed 9 May 2012), in European Medicines Agency, Opinion 2009.

  266. Kim MA, et al. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number. Histopathology. 2008;52(6):738–46.

    Article  CAS  PubMed  Google Scholar 

  267. Ayhan A, et al. Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas. Jpn J Cancer Res. 1994;85(6):584–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. Lee HK, et al. Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis. 2003;18(6):518–25.

    Article  PubMed  Google Scholar 

  269. Hattori Y, et al. K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes. Proc Natl Acad Sci U S A. 1990;87(15):5983–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Smith MG, et al. Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006;12(19):2979–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Wang L, et al. Disordered beta-catenin expression and E-cadherin/CDH1 promoter methylation in gastric carcinoma. World J Gastroenterol. 2006;12(26):4228–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Kuniyasu H, et al. Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem Biophys Res Commun. 1992;189(1):227–32.

    Article  CAS  PubMed  Google Scholar 

  273. Kozma L, et al. C-myc amplification and cluster analysis in human gastric carcinoma. Anticancer Res. 2001;21(1B):707–10.

    CAS  PubMed  Google Scholar 

  274. Calcagno DQ, et al. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma. World J Gastroenterol. 2006;12(38):6207–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Yasui W, et al. Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric carcinomas. Jpn J Cancer Res. 1997;88(7):625–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  276. Xiangming C, et al. The cooperative role of p27 with cyclin E in the prognosis of advanced gastric carcinoma. Cancer. 2000;89(6):1214–9.

    Article  CAS  PubMed  Google Scholar 

  277. Kim DH, et al. Reduced expression of the cell-cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma. Histopathology. 2000;36(3):245–51.

    Article  CAS  PubMed  Google Scholar 

  278. Akama Y, et al. Frequent amplification of the cyclin E gene in human gastric carcinomas. Jpn J Cancer Res. 1995;86(7):617–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pathology Department, IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Rossella Rotondo, Flavio Rizzolio, Tiziana Perin & Vincenzo Canzonieri

  2. Department of Molecular Sciences and Nanosystems, Ca’ Foscari University, Venice-Mestre, VE, Italy

    Flavio Rizzolio

  3. Department of Biology, Temple University, Philadelphia, PA, USA

    Flavio Rizzolio

  4. CRO Biobank, IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Tiziana Perin

  5. Medical Oncology Department, IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Massimiliano Berretta

  6. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

    Fabrizio Zanconati

  7. Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, Temple University, Philadelphia, PA, USA

    Antonio Giordano

  8. Department of Medicine, Surgery and Neuroscience, Anatomic Pathology Section, University of Siena, Siena, Italy

    Antonio Giordano

  9. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, TS, Italy

    Vincenzo Canzonieri

  10. CRO Biobank, IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Vincenzo Canzonieri

  11. Department of Biology, Temple University, Philadelphia, PA, USA

    Vincenzo Canzonieri

Authors
  1. Rossella Rotondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Flavio Rizzolio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiziana Perin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimiliano Berretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabrizio Zanconati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vincenzo Canzonieri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Antonio Giordano or Vincenzo Canzonieri .

Editor information

Editors and Affiliations

  1. Pathology Unit and Biobank, CRO-Aviano, IRCCS, National Cancer Institute, Aviano, Italy

    Vincenzo Canzonieri

  2. Sbarro Institute for Cancer, Research and Molecular Medicine, Department of Biology, Temple University, Philadelphia, PA, USA

    Antonio Giordano

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rotondo, R. et al. (2019). Pathological Diagnosis and Classification of Gastric Epithelial Tumours. In: Canzonieri, V., Giordano, A. (eds) Gastric Cancer In The Precision Medicine Era. Current Clinical Pathology. Humana, Cham. https://doi.org/10.1007/978-3-030-04861-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-04861-7_4

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-04860-0

  • Online ISBN: 978-3-030-04861-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation