Skip to main content
SpringerLink
Log in

Clinical Molecular Pathology

  • Chapter
  • First Online:
Gastric Cardiac Cancer

  • 720 Accesses

Abstract

Gastric cardiac carcinoma demonstrates much more complex molecular pathobiology than esophageal or distal gastric non-cardiac carcinomas. The most common molecular type is the chromosomal instable carcinoma that shows an increasing gradient from a low prevalence in the distal stomach to a high level in the gastric cardia and to the peak in the distal esophagus. Thus, esophageal adenocarcinoma is in fact part of gastric chromosomal instable carcinoma. In contrast, Epstein-Barr virus-related, microsatellite instable, and genomic stable carcinomas occur in gastric cardiac carcinoma, but not so or extremely rare in esophageal adenocarcinoma. The most important molecular target in gastric cardiac carcinoma is the HER2 gene, in addition to PD-1 and PD-L1, with significant therapeutic values to treat patients with advanced gastric cardiac carcinoma.

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
Softcover Book
USD 129.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.00
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. Huang Q, Sun Q, Fan XS, et al. Recent advances in proximal gastric carcinoma. J Dig Dis. 2016;17(7):421–32.

    Article  PubMed  Google Scholar 

  2. Huang Q, Shi J, Sun Q, et al. Clinicopathological characterisation of small (2 cm or less) proximal and distal gastric carcinomas in a Chinese population. Pathology. 2015;47:526–32.

    Article  PubMed  CAS  Google Scholar 

  3. Amini N, Spolverato G, Kim Y, et al. Clinicopathological features and prognosis of gastric cardia adenocarcinoma: a multi-institutional US study. J Surg Oncol. 2015;111:285–92.

    Article  PubMed  Google Scholar 

  4. Carneiro F, Moutinho C, Pera G, et al. Pathology findings and validation of gastric and esophageal cancer cases in a European cohort (EPIC/EUR-GAST). Scand J Gastroenterol. 2007;42:618–27.

    Article  PubMed  Google Scholar 

  5. Huang Q, Zhang LH. The histopathologic spectrum of carcinomas involving the gastroesophageal junction in the Chinese. Int J Surg Pathol. 2007;15:38–52.

    Article  PubMed  Google Scholar 

  6. Huang Q, Gold JS, Shi J, et al. Pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus. Hum Pathol. 2012;43:911–20.

    Article  PubMed  CAS  Google Scholar 

  7. Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer (review). Int J Oncol. 2015;46:1421–34.

    Article  PubMed  CAS  Google Scholar 

  8. Chen JN, He D, Tang F, Shao CK. Epstein-Barr virus-associated gastric carcinoma: a newly defined entity. J Clin Gastroenterol. 2012;46:262–71.

    Article  PubMed  CAS  Google Scholar 

  9. Lim H, Park YS, Lee JH, et al. Features of gastric carcinoma with lymphoid stroma associated with Epstein-Barr virus. Clin Gastroenterol Hepatol. 2015;13:1738–44.e2.

    Article  PubMed  Google Scholar 

  10. Taniere P, Martel-Planche G, Maurici D, et al. Molecular and clinical differences between adenocarcinomas of the esophagus and of the gastric cardia. Am J Pathol. 2001;158:33–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Wijnhoven BP, Siersema PD, Hop WC, et al. Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Esophageal Tumour Study Group. Br J Surg. 1999;86:529–35.

    Article  PubMed  CAS  Google Scholar 

  12. Shah MA, Khanin R, Tang L, et al. Molecular classification of gastric cancer: a new paradigm. Clin Cancer Res. 2011;17:2693–701.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Mocellin S, Verdi D, Pooley KA, Nitti D. Genetic variation and gastric cancer risk: a field synopsis and meta-analysis. Gut. 2015;64(8):1209–19.

    Article  PubMed  CAS  Google Scholar 

  14. Xue W, Zhu M, Wang Y, He J, Zheng L. Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis. Sci Rep. 2015;5:7986.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Sun CQ, Chang YB, Cui LL, et al. A population-based case-control study on risk factors for gastric cardia cancer in rural areas of Linzhou. Asian Pac J Cancer Prev. 2013;14:2897–901.

    Article  PubMed  Google Scholar 

  16. Jiang X, Tseng CC, Bernstein L, Wu AH. Family history of cancer and gastroesophageal disorders and risk of esophageal and gastric adenocarcinomas: a case-control study. BMC Cancer. 2014;14:60.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.

    Article  CAS  Google Scholar 

  18. Huang Q, Fan XS, Agoston AT, et al. Comparison of gastroesophageal junction carcinomas in Chinese versus American patients. Histopathology. 2011;59(2):188–97.

    Article  PubMed  Google Scholar 

  19. Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541(7636):169–75.

    Article  CAS  Google Scholar 

  20. Jia F, Teer JK, Knepper TC, et al. Discordance of somatic mutations between Asian and Caucasian patient populations with gastric cancer. Mol Diagn Ther. 2017;21(2):179–85. https://doi.org/10.1007/s40291-016-0250-z.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Bang YJ, Van Cutsem E, Feyereislova A, 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, randomized controlled trial. Lancet. 2010;376(9742):687–97.

    Article  PubMed  CAS  Google Scholar 

  22. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.

    Article  PubMed  CAS  Google Scholar 

  23. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    Article  PubMed  CAS  Google Scholar 

  24. Bang YJ. Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer. J Clin Gastroenterol. 2012;46:637–48.

    Article  PubMed  CAS  Google Scholar 

  25. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18:476–84.

    Article  CAS  PubMed  Google Scholar 

  26. Kim WH, Gomez-Izquierdo L, Vilardell F, et al. HER2 status in gastric and gastroesophageal junction cancer: results of the large, multinational HER-EAGLE Study. Appl Immunohistochem Mol Morphol. 2018;26(4):239–245.

    Google Scholar 

  27. Kwak H, Khor TS, Alpert L, et al. HER2 expression is predominantly negative in GEJ and gastric adenocarcinoma with signet ring cell differentiation; Study of 346 cases modern pathology. 2017;30(Suppl 2s):180A–1A.

    Google Scholar 

  28. Feng XS, Wang YF, Hao SG, Ru Y, Gao SG, Wang LD. Expression of Das-1, Ki67 and sulfuric proteins in gastric cardia adenocarcinoma and intestinal metaplasia lesions. Exp Ther Med. 2013;5:1555–8.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Birkman EM, Algars A, Lintunen M, Ristamaki R, Sundstrom J, Carpen O. EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus. BMC Cancer. 2016;16:406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Wang CW, Fang XH. The role of targeted agents in the treatment of advanced gastric cancer: a meta-analysis of randomized controlled trials. Eur Rev Med Pharmacol Sci. 2016;20(9):1725–32.

    PubMed  Google Scholar 

  31. Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446–64.

    Article  PubMed  CAS  Google Scholar 

  32. Kinugasa H, Nouso K, Tanaka T, et al. Droplet digital PCR measurement of HER2 in patients with gastric cancer. Br J Cancer. 2015;112(10):1652–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 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. Lyon: IARC Press; 2010. p. 48–58.

    Google Scholar 

  34. Saito R, Abe H, Kunita A, Yamashita H, Seto Y, Fukayama M. Overexpression and gene amplification of PD-L1 in cancer cells and PD-L1(+) immune cells in Epstein-Barr virus-associated gastric cancer: the prognostic implications. Mod Pathol. 2017;30(3):427–39. https://doi.org/10.1038/modpathol.2016.202.

    Article  PubMed  CAS  Google Scholar 

  35. Jenkins TM, Tondon R, Wang LP, et al. Mismatch repair deficiency (MMR-D) and programmed death ligand (PD-L1) expression in gastric adenocarcinoma. Mod Pathol. 2017;30(Suppl 2s):178A.

    Google Scholar 

  36. Xing X, Jia S, Wu J, et al. Clonality analysis of synchronous gastroesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing. J Pathol. 2017;243(2):165–75. https://doi.org/10.1002/path.4932.

    Article  PubMed  CAS  Google Scholar 

  37. Savant D, Vitkovski T, Thomas R, Rishi A. Programmed cell death ligand-1 (PD-L1) expression in gastrointestinal stromal tumors correlates significantly with presence of tumor infiltrating lymphocytes. Mod Pathol. 2017;30(Suppl 2s):199A.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China

    Xiangshan Fan

  2. Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, West Roxbury, MA, USA

    Qin Huang

  3. Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA

    Qin Huang

Authors
  1. Xiangshan Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Harvard Medical School/Brigham and Women’s Hospital, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts, USA

    Qin Huang

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fan, X., Huang, Q. (2018). Clinical Molecular Pathology. In: Huang, Q. (eds) Gastric Cardiac Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-79114-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-79114-2_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-79113-5

  • Online ISBN: 978-3-319-79114-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation