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Category: Volume 08 Issue 04 April 2020
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Title: Significance of HER 2/neu in Gastric Adenocarcinomas - A Clinico-pathological correlation

Authors: Dr Debahuti Mohapatra, Dr Kaushambi Chakraborty, Dr Debasmita Das, Dr Rupanita Biswal

 DOI: https://dx.doi.org/10.18535/jmscr/v8i4.86

Abstract

   

Background: Gastric cancers are the fifth most common cancer and the third most common cause of cancer mortality, in which adenocarcinoma tops the list. Human epidermal growth factor receptor 2 (Her2/neu), a proto-oncogene on amplification leads to various human cancers, namely breast, colon, cervical, endometrial, urothelial and recently discovered gastric adenocarcinoma.

Material and Methods: A prospective study was conducted in the Department of Pathology of a tertiary care hospital, Bhubaneswar, Odisha from January 2015 to December 2017. Endoscopic, total, distal and partial gastrectomy specimens were included after clinico-radiological data collection. The exclusion criterion was biopsies received post neo-adjuvant therapy.

Her2/neu immunohistochemistry (IHC) was conducted on all the adenocarcinoma of gastric/ gastro-esophageal location and was scored as 0, 1+, 2+ and 3+ (absent, mild, moderate and strong positivity).

Observation: It was found that gastric antrum was the commonest location followed by body and gastroesophageal junction. According to histological types, classical intestinal type showed maximum Her2/neu positivity followed by papillary, signet ring cell type while diffuse type showed least positivity.Though most of the strong Her2/neu adenocarcinomas were well differentiated type but majority of them presented with lymphnode metastasis.

Conclusion: In developing countries, the mortality due to gastric adenocarcinoma is high. The study aims at the prevalence of Her2/neu positivity in various sites, types, grade and stage of gastric adenocarcinomas to facilitate the institution of targeted therapy (anti-Her2/neuAb, Transtuzumab) in order to see its effect on patients’ morbidity and mortality.

Keywords: Gastric Adenocarcinoma, Her2/neu, Transtuzumab.

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136:359-86.
  2. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 1986; 232:1644-6.
  3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-82.
  4. Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z, Kurzrock R. HER2 expression status in diverse cancers: review of results from 37,992 patients. Cancer Metastasis Rev 2015; 34: 157-64.
  5. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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, randomised controlled trial. Lancet 2010; 376:687-97.
  6. Wong DD, de Boer WB, Platten MA, Jo VY, Cibas ES, Kumarasinghe MP. HER2 testing in malignant effusions of metastatic gastric carcinoma: is it feasible? Diagn Cytopathol 2015; 43: 80-5.
  7. Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797–805.
  8. Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010; 457: 299-307.
  9. Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. AdvAnatPathol 2011; 18: 53-9.
  10. Yonemura Y, Ninomiya I,  Yamaguchi A, Fushida S, Kiimini H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short-term prognosis in gastric cancer. Cancer Res 1991;51:1034-8.
  11. Ishida T, Tsujisaki M,  Hanzawa Y,Hirakawa T, Hinoda Y, Imai K, et al. Significance of erbB-2 gene product as a target molecule for cancer therapy, Scand J Immunol 1994;39: 459-66
  12. Tokunaga A, Onda M,  Okuda T, Teramoto T, Fujita I, Mizutani T, et al. Clinical significance of epidermal growth factor (EGF), EGF receptor and c-erbB-2 in human gastric cancer. Cancer 1995;75:1418-25.
  13. Yano T, Ochiai A, Doi T. Expression of HER2 in gastric cancer: comparison between protein expression and gene amplification using a new commercial kit. J ClinOncol 2004;22:14.
  14. Laboissiere RS, Buzelin MA, Balabram D,Brot MD, Nunes CB, Rocha RM et al. Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections. BMC Gastroenterol 2015;15:157.
  15. Lordick F, Bang YJ,  Kang YK, Otero Reyes D, Manikhas GM, Shen L, et al. HER2-positive advanced gastric cancer: similar HER2-positivity levels to breast cancer. Eur J Cancer2007;5:272.
  16. Gravalos, C., Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol2008;19:1523–1529.
  17. Park DI, Yun JW, Park JH, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer, Dig Dis Sci2006; 51:1371-9.
  18. Tanner M, Hollmen M,  Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIa gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab, Ann Oncol 2005;16: 273-8.
  19. Shan L, Ying J, Lu N. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol2013; 8:76.

Corresponding Author

Dr Kaushambi Chakraborty

Senior Resident, Department of Pathology, ESI-PGIMSR, Medical College & Hospital, Joka, Kolkata