Overexpression of Her2/Neu in Gastric Carcinoma: association with histological type, tumor grade and H. Pylori infection

  • Piyali Ghosh
  • Indranil Chakrabarti Department of Pathology, North Bengal Medical College, Darjeeling,West Bengal
  • Sourav Bhowmick
  • Mimi Gangopadhyay
  • Mamata Guha Mallick Sinha
  • Sudip Bhattacharya
Keywords: Gastric carcinoma, HER2, Helicobacter pylori

Abstract

Introduction: Gastric cancer is the second leading cause of cancer mortality in the world and its management, especially in advanced stages, has evolved relatively little. In particular, no targeted modality has so far been incorporated for treatment. HER2 over-expression is increasingly recognized as a frequent molecular abnormality, driven as in breast cancer by gene amplification. There is mounting evidence of the role of HER2 over-expression in patients with gastric cancer, and it has been strongly correlated to poorer outcomes and a more aggressive disease.Aims and objective: The purpose of this study is to establish the clinicoepidemiological, histopathological and immunohistochemical particularities of the gastric carcinomas, and to identify the factors with a prognostic value.Methods: The present study included 54 cases of gastric carcinoma, who had undergone endoscopy guided biopsy or gastrectomy. Expression of HER2 oncoprotein by immunohistochemistry and detection of  Helicobacter pylori was done using modified Giemsa stain. Expression of HER2 was correlated with patient’s clinicopathological parameters.Results: HER2+ rates were 22.22% (12/54). HER2 over-expression was associated with poorly differentiated carcinoma (P = 0.0159) and intestinal type of gastric carcinoma (P=0.0245).Conclusion: In this study, HER2 expression was seen more in intestinal type of gastric carcinoma as compared to the diffuse type involving mostly poorly differentiated cases. Regarding H. pylori, we found no correlation between its presence and the over-expression of HER2. So, the results of this study may contribute to a better knowledge of the efficacy of trastuzumab-based therapy in HER2 positive gastric cancers but the outcome of anti H. pylori medication in HER2 positive cases still remain inconclusive. 

References

1. Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol 2012;3(3):251-61
2. Parkin DM. International variation. Oncogene 2004; 23:6329-40.
3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127:2893-917.
4. Wang S, Zheng G, Chen L, Xiong B. Effect of HER-2/neu Over-expression on Prognosis in Gastric Cancer: A Meta-analysis. Asian Pacific J Cancer Prev; 12:1417-23.
5. Meza-Junco J, Sawyer MB. Metastatic gastric cancer - focus on targeted therapies. Biologics 2012; 6:137–46.
6. Han HS, Lauwers GY. Gastric Carcinoma. Available from- http://www.dako.com/28830_14dec10_connection15_ HER2 in Gastric cancer.pdf.
7. 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.
8. Selcukbiricik F, Tural D, Erdamar S, Buyukunal E, Demirelli F, Serdengecti S.Is Helicobacter pylori a poor prognostic factor for HER-2 SISH positive gastric cancer? Asian Pac J Cancer Prev. 2013;14(5):3319-22.
9. Yu GZ, Chen Y, Wang JJ. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance, J Cancer Res Clin Oncol, 2009, 135(10):1331–39.
10. Moelans CB, Milne AN, Morsink FH, Offerhaus GJ, van Diest PJ. Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol 2011; 34: 89-95.
11. Bădescu A, Georgescu CV, Vere CC, Crăiţoiu S, Grigore D.Correlations between HER2 oncoprotein, VEGF expression, MVD and clinicopathological parameters in gastric cancer. Rom J Morphol Embryol 2012; 53(4):997–1005.
12. Sekaran A, Kandagaddala RS, Darisetty S, Lakhtakia S, Ayyagari S, Rao GV, et al. HER2 expression in gastric cancer in Indian population-An immunohistochemistry and fluorescence in situ hybridization study. Indian J Gastroenterol. 2012; 31(3):106-10.
13. Federica Grillo, Matteo Fassan, Chiara Ceccaroli, Cinzia Giacometti, Monica Curto, Vittorina Zagonel et al. The reliability of endoscopic biopsies in assessing HER2 status in gastric and gastroesophageal junction cancer: a study comparing biopsies with surgical samples. Translational Oncology,2013;6(1):10-16.
14. Slesak B, Harlozinska A, Porebska I, Bojarowski T, Lapinska J, Rzeszutko M,et al. Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. Anticancer Res 1998;18:2727-32.
15. Takehana T, Kunitomo K, Kono K, Kitahara F, Iizuka H, Matsumoto Y et al. Status of c-erbB-2 in gastric adeno¬carcinoma: a comparative study of immunohistochemis¬try, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. Int J Cancer 2002;98:833-7.
16. Kim KC, Koh YW, Chang HM, Kim TH, Yook JH, Kim BS et al. Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol 2011; 18, 2833–40.
17. Jan Trøst Jørgensen, Maria Hersom. HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature. Journal of Cancer 2012; 3: 137-44.
18. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Yet al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005; 16:273–78.
19. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51(8):1371-9
20. Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg. 2009 Oct;33(10):2112-8.
21. Cidon EU, Centeno RG, Lagarto EG, Peral JI. HER-2 Evaluation in a Specific Gastric Cancer Population with the Highest Rate of Mortality in Spain, J Oncol 2011; 2011:391564.
Published
2016-08-17
Section
Original Article