Advertisement

Clinical Molecular Pathology

  • Xiangshan Fan
  • Qin Huang
Chapter

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.

Keywords

Gastric cardiac carcinoma Gastric cancer Stomach Cancer HER2 PD-1 PD-L1 

References

  1. 1.
    Huang Q, Sun Q, Fan XS, et al. Recent advances in proximal gastric carcinoma. J Dig Dis. 2016;17(7):421–32.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 7.
    Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer (review). Int J Oncol. 2015;46:1421–34.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Shah MA, Khanin R, Tang L, et al. Molecular classification of gastric cancer: a new paradigm. Clin Cancer Res. 2011;17:2693–701.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.CrossRefGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541(7636):169–75.CrossRefGoogle Scholar
  20. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 22.
    Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 24.
    Bang YJ. Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer. J Clin Gastroenterol. 2012;46:637–48.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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. 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.CrossRefPubMedGoogle Scholar
  35. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Xiangshan Fan
    • 1
  • Qin Huang
    • 2
    • 3
  1. 1.Department of PathologyThe Affiliated Drum Tower Hospital, Nanjing University Medical SchoolNanjing, JiangsuPeople’s Republic of China
  2. 2.Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare SystemWest RoxburyUSA
  3. 3.Harvard Medical School and Brigham and Women’s HospitalBostonUSA

Personalised recommendations