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The Pathologist and the Phenotype of Hereditary Colorectal Cancer

  • Jeremy R. JassEmail author
Chapter
Part of the M.D. Anderson Solid Tumor Oncology Series book series (MDA, volume 5)

Abstract

The aim of this review is not to provide a morphological description of each form of colorectal cancer family syndrome. The aim is to explain to a readership that is mainly from a non-pathology background why, when faced with a tissue sample or surgical specimen, it is extremely difficult to extract information that is comprehensive and maximizes the potential for informing the clinical and basic science researcher as well as guiding clinical management. The usual description of a colorectal tumor focuses on its histogenetic type. However, the microscopic appearances of polyps and cancers in cancer family syndromes frequently differ from the appearances of their sporadic counterparts. Even before considering these differences, it is necessary to deconstruct the formal description of biopsied or resected surgical specimens into its basic elements. With respect to polyps, the parameters in question include size, macroscopic appearances, number, anatomic location, and even the synthesis of findings accumulating over time. In critically analyzing these parameters, including the mechanisms underlying their marked phenotypic variation, the full scale of task faced by the pathologist is brought into focus.

Keywords

Colon Cancer Pathology Phenotype Diagnosis 

References

  1. 1.
    Bussey HJR. Familial Polyposis Coli. Baltimore, MD: Johns Hopkins Press; 1975.Google Scholar
  2. 2.
    Jass JR. Colorectal adenomas in surgical specimens from subjects with hereditary non-polyposis colorectal cancer. Histopathology. 1995;27:263–7.PubMedCrossRefGoogle Scholar
  3. 3.
    De Jong AE, Morreau H, van Puijenbroek M, Eilers PHC, Wijnen J, Nagengast FM, et al. The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology. 2004;126:42–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Lynch HT, Smyrk T, Jass JR. Hereditary nonpolyposis colorectal cancer and colonic adenomas: aggressive adenomas? Semin Surg Oncol. 1995;11:406–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Vasen HFA, Nagengast FM, Meera Khan P. P. Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome). Lancet. 1995;345:1183–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Jass JR, Stewart SM. Evolution of hereditary non-polyposis colorectal cancer. Gut. 1992;33:783–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Hamilton SR, Aaltonen LA. World Health Organization classification of tumours. Pathology and genetics. Lyon: IARC Press; 2000.Google Scholar
  8. 8.
    Morson BC. Some peculiarities in the histology of intestinal polyps. Dis Colon Rectum. 1962;5:337–44.CrossRefGoogle Scholar
  9. 9.
    Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer. 1975;36(6):2251–70.PubMedCrossRefGoogle Scholar
  10. 10.
    Bird RP. Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett. 1987;37(2):147–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Bird RP, McLellan EA, Bruce WR. Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer. Cancer Surv. 1989;8(1):189–200.PubMedGoogle Scholar
  12. 12.
    Roncucci L, Medline A, Bruce WR. Classification of aberrant crypt foci and microadenomas in human colon. Cancer Epidemiol Biomarkers Prev. 1991;1:57–60.PubMedGoogle Scholar
  13. 13.
    Roncucci L, Stamp D, Medline A, Cullen JB, Bruce WR. Identification and quantification of aberrant crypt foci and microadenomas in the human colon. Hum Pathol. 1991;22:287–94.PubMedCrossRefGoogle Scholar
  14. 14.
    Rosenberg DW, Yang S, Pleau DC, Greenspan EJ, Steven RG, Rajan TV, et al. Mutations of BRAF and KRAS differentially distinguish serrated versus non-serrated hyperplastic aberrant crypt foci in humans. Cancer Res. 2007;67:3551–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Jen J, Powell SM, Papadopoulos N, Smith KJ, Hamilton SR, Vogelstein B, et al. Molecular determinants of dysplasia in colorectal lesions. Cancer Res. 1994;54:5523–6.PubMedGoogle Scholar
  16. 16.
    Lamlum H, Papadopoulou A, Ilyas M, Rowan A, Gillet C, Hanby A, et al. APC mutations are sufficient for the growth of early colorectal adenomas. Proc Natl Acad Sci U S A. 2000;97:2225–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Shih I-M, Wang TL, Traverso G, Romans K, Hamilton SR, Ben-Sasson S, et al. Top-down morphogenesis of colorectal tumors. Proc Natl Acad Sci U S A. 2001;98(5):2640–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Preston SL, Wong W-D, Chan AO-O, Poulsom R, Jeffery R, Goodlad RA, et al. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and intial expansion by crypt fission. Cancer Res. 2003;63:3819–25.PubMedGoogle Scholar
  19. 19.
    Jass JR, Whitehall VLJ, Young J, Leggett BA. Emerging concepts in colorectal neoplasia. Gastroenterology. 2002;123:862–76.PubMedCrossRefGoogle Scholar
  20. 20.
    Nakamura S, Kino I. Morphogenesis of minute adenomas in familial polyposis coli. J Natl Cancer Inst. 1984;73:41–9.PubMedGoogle Scholar
  21. 21.
    Sakashita M, Aoyama N, Maekawa S, Kuroda K, Shirasaka D, Ichihara T, et al. Flat-elevated and depressed subtypes of flat early colorectal cancers should be distinguished by their pathological features. Int J Colorectal Dis. 2000;15:275–81.PubMedCrossRefGoogle Scholar
  22. 22.
    Umetani N, Sasaki S, Masaki T, Watanabe T, Matsuda K, Muto T. Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis. Br J Cancer. 2000;82(1):9–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Yamagata S, Muto T, Uchida Y, Masaki T, Sawada T, Tsuno N, et al. Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in polypoid adenomas. Jpn J Cancer Res. 1994;85:147–51.PubMedCrossRefGoogle Scholar
  24. 24.
    Nosho K, Yamamoto H, Adachi Y, Endo T, Hinoda Y, Imai K. Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis. Br J Cancer. 2005;92:1193–200.PubMedCrossRefGoogle Scholar
  25. 25.
    Maltzman T, Knoll K, Martinez ME, Byers T, Stevens BR, Marshall JR, et al. Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics. Gastroenterology. 2001;121:302–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology. 1985;89(2):328–36.PubMedGoogle Scholar
  27. 27.
    Muto T, Kamiya J, Sawada T, Konishi F, Sugihara K, Kubota Y, et al. Small “flat adenoma” of the large bowel with special reference to its clinicopathologic features. Dis Colon Rectum. 1985;28(11):847–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC−/− colon carcinoma. Science. 1997;275(5307):1784–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Lamlum H, Ilyas M, Rowan A, Clark S, Johnson V, Bell JA, et al. The type of somatic mutation of APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson’s “two-hit” hypothesis. Nat Med. 1999;5:1071–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Albuquerque C, Breukel C, van der Luijt R, Fidalgo P, Lage P, Slors FJ, et al. The “just-right” signaling model: APC somatic mutations are selected based on a specific level of activation of the beta-catenin signaling cascade. Hum Mol Genet. 2002;11:1549–60.PubMedCrossRefGoogle Scholar
  31. 31.
    Lanspa SJ, Lynch HT, Smyrk TC, Strayhorn P, Watson P, Lynch JF, et al. Colorectal adenomas in the Lynch syndromes. Results of a colonoscopy screening programme. Gastroenterology. 1990;98:1117–22.PubMedGoogle Scholar
  32. 32.
    Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993;75:951–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Sieber OM, Segditsas S, Knudsen AL, Zhang J, Rowan AJ, Spain SL, et al. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006;55:1440–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Spirio LN, Samowitz W, Robertson J, Roberston M, Burt RW, Leppert M, et al. Alleles of APC modulate the frequency and classes of mutations that lead to colon polyps. Nat Genet. 1998;20:385–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Su LK, Barnes CJ, Yao W, Qi Y, Lynch PM, Steinbach G. Inactivation of germline mutant APC alleles by attenuated somatic mutations: a molecular genetic mechanism for attenuated familial adenomatous polyposis. Am J Hum Genet. 2000;67:582–90.PubMedCrossRefGoogle Scholar
  36. 36.
    Wallace MH, Frayling IM, Clark SK, Neale K, Phillips RKS. Attenuated adenomatous polyposis coli: the role of ascertainment bias through dye-spray at colonoscopy. Dis Colon Rectum. 1999;42:1078–80.PubMedCrossRefGoogle Scholar
  37. 37.
    Kambara T, Simms LA, Whitehall VLJ, Spring KJ, Wynter C, Walsh MD, et al. BRAF mutation and CpG island methylation: an alternative pathway to colorectal cancer. Gut. 2004;53:1137–44.PubMedCrossRefGoogle Scholar
  38. 38.
    O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, et al. Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol. 2006;30:1491–501.PubMedCrossRefGoogle Scholar
  39. 39.
    Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65:6063–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Vandrovcova J, Lagerstedt-Robinsson K, Pahlman L, Lindblom A. Somatic BRAF-V600E mutations in familial colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:2270–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Young J, Barker MA, Simms LA, Walsh MD, Biden KG, Buchanan D, et al. BRAF mutation and variable levels of microsatellite instability characterize a syndrome of familial colorectal cancer. Clin Gastroenterol Hepatol. 2005;3:254–63.PubMedCrossRefGoogle Scholar
  42. 42.
    Young J, Jass JR. The case for a genetic predisposition to serrated neoplasia of the colorectum: Hypothesis and review of the literature. Cancer Epidemiol Biomarkers Prev. 2006;15:1778–84.PubMedCrossRefGoogle Scholar
  43. 43.
    Minoo P, Baker K, Goswami R, Chong G, Foulkes WD, Ruszkiewicz AR, et al. Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis. Gut. 2006;55:1467–74.PubMedCrossRefGoogle Scholar
  44. 44.
    Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol. 2003;27:65–81.PubMedCrossRefGoogle Scholar
  45. 45.
    Burt RW, Jass JR. Hyperplastic polyposis. In: Hamilton SR, Aaltonen LA, editors. WHO Classification of Tumours. Pathology and genetics. Tumours of the digestive system. Berlin: Springer-Verlag; 2000.Google Scholar
  46. 46.
    Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110:748–55.PubMedCrossRefGoogle Scholar
  47. 47.
    Jeevaratnam P, Cottier DS, Browett PJ, Van de Water NS, Pokos V, Jass JR. Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome. J Pathol. 1996;179:20–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Chow E, Lipton L, Lynch E, D’Souza R, Aragona C, Hodgkin L, et al. Hyperplastic polyposis: Phenotypic presentations and the role of MBD4 and MYH. Gastroenterology. 2006;131:30–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Arthur JF. Structure and significance of metaplastic nodules in the rectal mucosa. J Clin Pathol. 1968;21:735–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Biemer-Hüttmann A-E, Walsh MD, McGuckin MA, Ajioka Y, Watanabe H, Leggett BA, et al. Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum. J Histochem Cytochem. 1999;47:1039–47.PubMedCrossRefGoogle Scholar
  51. 51.
    Jass JR, Filipe MI, Abbas S, Falcon CA, Wilson Y, Lovell D. A morphologic and histochemical study of metaplastic polyps of the colorectum. Cancer. 1984;53(3):510–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Minoo P, Jass JR. Senescence and serration: a new twist to an old tale. J Pathol. 2006;210:137–40.PubMedCrossRefGoogle Scholar
  53. 53.
    Yang S, Farraye FA, Mack C, Posnik O, O’Brien MJ. BRAF and KRAS mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status. Am J Surg Pathol. 2004;28:1452–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Wynter CVA MDW, Higuchi T, Leggett BA, Young J, Jass JR. Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut. 2004;53:573–80.CrossRefGoogle Scholar
  55. 55.
    Iino H, Jass JR, Simms LA, Young J, Leggett B, Ajioka Y, et al. DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer? J Clin Pathol. 1999;52:5–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Williams GT. Metaplastic (hyperplastic) polyps of the large bowel: benign neoplasms after all? Gut. 1997;40:691–2.PubMedGoogle Scholar
  57. 57.
    Jass JR, Williams CB, Bussey HJR, Morson BC. Juvenile polyposis – a precancerous condition. Histopathology. 1988;13:619–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14:524–37.PubMedCrossRefGoogle Scholar
  59. 59.
    Urbanski SJ, Marcon N, Kossakowska AE, Bruce WR. Mixed hyperplastic adenomatous polyps – An underdiagnosed entity. Report of a case of adenocarcinoma arising within a mixed hyperplastic adenomatous polyp. Am J Surg Pathol. 1984;8:551–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Snover DC, Jass JR, Fenoglio-Preiser C, Batts KP. Serrated polyps of the large intestine. A morphologic and molecular review of an evolving concept. Am J Clin Pathol. 2005;124:380–91.PubMedCrossRefGoogle Scholar
  61. 61.
    Jass JR. Serrated route to colorectal cancer: back street or super highway? J Pathol. 2001;193:283–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Jass JR. Serrated adenoma of the colorectum. Curr Diagn Pathol. 2002;8:42–9.CrossRefGoogle Scholar
  63. 63.
    Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Makinen MJ. Colorectal serrated adenocarcinoma. Histopathology. 2007;50:131–50.PubMedCrossRefGoogle Scholar
  65. 65.
    Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Jass JR, Baker K, Zlobec I, Higuchi T, Barker M, Buchanan D, et al. Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a “fusion” pathway to colorectal cancer. Histopathology. 2006;49:121–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, et al. Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol. 2001;159:2107–16.PubMedCrossRefGoogle Scholar
  68. 68.
    Jass JR, Walsh MD, Barker M, Simms LA, Young J, Leggett BA. Distinction between familial and sporadic forms of colorectal cancer showing DNA microsatellite instability. Eur J Cancer. 2002;38:858–66.PubMedCrossRefGoogle Scholar
  69. 69.
    Jass JR, Do K-A, Simms LA, Iino H, Wynter C, Pillay SP, et al. Morphology of sporadic colorectal cancer with DNA replication errors. Gut. 1998;42:673–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994;145:148–56.PubMedGoogle Scholar
  71. 71.
    Greenson JK, Bonner JD, Ben-Yzhak O, Cohen HI, Miselvich I, Resnick MB, et al. Phenotype of microsatellite unstable colorectal carcinomas. Am J Surg Pathol. 2003;27:563–70.PubMedCrossRefGoogle Scholar
  72. 72.
    Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal cancer. Cancer. 2001;91:2417–22.PubMedCrossRefGoogle Scholar
  73. 73.
    Jenkins MA, Hayashi S, O’Shea A-M, Burgart LJ, Smyrk TC, Shimuzu D, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology. 2007;133(1):48–56.PubMedCrossRefGoogle Scholar
  74. 74.
    Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20(4):1043–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Whitelaw SC, Murday VA, Tomlinson IPM, Thomas HJW, Cottrell S, Ginsberg A, et al. Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology. 1997;112:327–34.PubMedCrossRefGoogle Scholar
  76. 76.
    Carlson GJ, Nivatvongs S, Snover DC. Colorectal polyps in Cowden’s disease (multiple hamartoma syndrome). Am J Surg Pathol. 1984;8:763–70.PubMedCrossRefGoogle Scholar
  77. 77.
    Leggett BA, Devereaux B, Biden K, Searle J, Young J, Jass J. Hyperplastic polyposis: association with colorectal cancer. Am J Surg Pathol. 2001;25(2):177–84.PubMedCrossRefGoogle Scholar
  78. 78.
    Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, et al. Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res. 2003;63:7595–9.PubMedGoogle Scholar
  79. 79.
    Olschwang S, Serova-Sinilnikova OM, Lenoir GM, Thomas G. PTEN germ-line mutations in juvenile polyposis coli. Nat Genet. 1998;18:12–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Cao X, Eu KW, Kumarasinghe MP, Li HH, Loi C, Cheah PY. Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BPMR1A loss of function. J Med Genet. 2006;43:e13.PubMedCrossRefGoogle Scholar
  81. 81.
    Sweet K, Willis J, Zhou X-P, Gallione C, Sawada T, Alhopuro P, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294:2465–73.PubMedCrossRefGoogle Scholar
  82. 82.
    Mendelsohn G, Diamond MP. Familial ganglioneuromatous polyposis of the large bowel. Report of a family with associated juvenile polyposis. Am J Surg Pathol. 1984;8(7):515–20.PubMedCrossRefGoogle Scholar
  83. 83.
    Weidner N, Flanders DJ, Mitros FA. Mucosal ganglioneuromatosis associated with multiple colonic polyps. Am J Surg Pathol. 1984;8(10):779–86.PubMedCrossRefGoogle Scholar
  84. 84.
    Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, de Blois MC, et al. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet. 2006;78:1066–74.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Cellular PathologySt Mark’s Hospital & Imperial CollegeLondonUK

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