Clinicopathological Significance of HER2/neu Expression in Gastric Carcinoma
Keywords:
Gastric carcinoma, HER2/neu, immunohistochemistry, clinicopathological
Abstract
Background: Gastric cancer remains the most common cause of cancer related death worldwide. HER2/neu protein overexpression in gastric carcinoma was found to be an independent indicator of poor prognosis. The present study was designed to evaluate the frequency of HER2/neu expression in gastric carcinoma, and also the relationship between HER2/neu expression with clinicopathological parameters. Methods: Analysis of HER2/neu expression was done by immunohistochemistry in 41 specimens of Gastric carcinoma over a period of one year and was correlated with clinicopathological parameters. Samples with IHC score 2+ and 3+ were taken as HER2 positive. Result: The study revealed 15 (36.6%) cases of gastric carcinoma being positive for HER2/neu. Of the 41 cases, 5 were classified as score 3+ (12.2%), 10 were classified as score 2+ (24.4%), 11 were classified as score 1+ (26.8%) and 15 were classified as score 0 (36.6%). Peak incidence was found in the age group of 41-50 years. Significant correlation of HER2/neu expression was found with intestinal type (p-value=0.003) and also with moderately differentiated type (p-value=0.018) of gastric adenocarcinoma. However, no significant correlation was found with the other clinicalpathological parameters like age, sex, site, lymph node status and staging. Conclusion: HER-2/neu over-expression was significantly associated with intestinal type and moderately differentiated gastric carcinoma. HER2/neu status can be considered as an important prognostic factor in gastric carcinoma.References
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2. Lauwers GY, Carneiro F, Graham DY, Curado MP, Franceschi S, Montgomery E et al. Gastric carcinoma. Tumours of the stomach. WHO classification of Tumours of the Digestive System. 4th ed. Bosman F CFHRTN, editor: IARC Lyon; 2010.
3. Singh K, Ghoshal UC. Causal role of Helicobacter pylori infection in gastriccancer: An Asian enigma. World J Gastroenterol. 2006 Mar 7; 12(9): p. 1346-1351.
4. Dixit PR et al. in Epidemiological review of gastric cancer in India. Indian Journal of Medical & Paediatric Oncology. 2011 Jan-Mar; 32(1): p. 3–11.
5. Rosai J. Gastrointestinal tract-Stomach. Rosai and Ackerman’s Surgical Pathology. Vol-1, 10th ed. Missouri: MOSBY; 2011.
6. Rosai J. Breast. Rosai and Ackerman’s Surgical Pathology. Vol-2,10th ed. Missouri: MOSBY; 2011.
7.
Yu D, Hung MC. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 2000; 19: p. 6115–6121.
8. Hogdall EV, Christensen L, Kjaer SK, Blaakaer J, Bock JE, Glud E et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian cancer study. cancer. 2003; 98: p. 66-73.
9. Wang L, Habuchi T, Takahashi T, Kamoto T, Zuo T, Mitsumori K, et al. No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer. Int J Cancer. 2002; 97: p. 787–790.
10. Ruschoff 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: p. 299–307.
11. 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: p. 797–805.
12. Gürel S, Dolar E, Yerci O, Samli B, Oztürk H, Nak SG, et al. The relationship between c-erbB-2 oncogene expression and clinicopathological factors in gastric cancer. J Int Med Res. 1999; 27: p. 74–78.
13. Smith I, Procter M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007; 369(9555): p. 29–36.
14. Van Cutsem et al. Efficacy results from the ToGA trial: A phase III study of trastruzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). ASCO Abstract LBA. 2010.
15. Rajagopal I, Niveditha SR, Sahadev R, Nagappa PK and Rajendra SG. HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas. J Clin Diagn Res. 2015 March; 9(3): p. 6-10.
16. Gordon MA, Gundacker HM, Benedetti J, Macdonald JS, Baranda JC, Levin WJ e al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Press Ann Oncol. 2013 July; 24(7): p. 1754–1761.
17. Tewari M, Kumar A, Mishra RR, KumarM and Shukla HS. HER2 Expression in Gastric and Gastroesophageal Cancer: Report from a Tertiary Care Hospital in North India. Indian J Surg. 2013.
18. Yan SY, Hu Y, Fan JG, Tao GQ, Lu YM, Cai X et al. Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World J Gastroenterol. 2011 March; 17(11): p. 1501–150.
19. Barros-Silva JD, Leitao D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. British Journal of Cancer. 2009; 100: p. 487-493.
20. Raziee HR, Kermani TA, Ghaffarzadegan K , Shakeri T and Ghavamnasiri MR. HER-2/neu expression in resectable gastric cancer and its relationship with histolopathologic subtype , grade and stage. Iranian Journal of Basic Medical Sciences. 2007; 10(2): p. 139-145.
21. Tanner et al. Amplification of HER2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.. Ann Oncol. 2005; 16: p. 2273-278.
22. Movagharnejad K, Sharbatdaran M, Sheffaee S, Kashifard M,and Sedagha S. HER-2/neu Marker Examination using Immunohistochemical Method in Patients Suffering from Gastric Adenocarcinoma. Int J Mol Cell Med. 2013 Autumn; 2(4): p. 199–203.
23. Gomez-Martin C, Garralda E, Echarri MJ, Ballesteros A, ArcedianoA, JRodríguez-Peralto JL et al. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol. 2012 August; 65(8): p. 751-757.
24. Shan L, Ying J and Lu N. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagnostic Pathology. 2013; 8: p. 76
Published
2019-09-27
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