Document Type : Original Article

Authors

1 Associate Professor of Internal Medicine , Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

2 Assistant Professor, Pathology and stem cells Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Professor of Internal Medicine ,Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

4 Faculty of medicine , Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background:In tumoral cells, the HER-2/Neu is an oncogene and overexpression would result in further membranous proteins. The role of this gene is known in ling and breast cancers. This study was undertaken to determine the HER-2/Neu overexpression in gastrectomy samples in patients with gastric cancer and its association with tumor histopathology prognostic factors.
Methods: This cross-sectional study was conducted among 48 samples of gastric cancer under gastrectomy. The slides were prepared to assess HER-2/Neu stained by IHC method (Biogenax Kit and DAOK criteria). Statistical analysis was done using SPSS software version 20.0.
Results: Out of 48 cases, 79.2% were males. The mean age was 59.93 ± 13.95 years and the mean tumor size was 5.5 ± 2.45 cm. Majority of cases were in anthrum and pylor (43.8%). Lauren class showed a higher frequency of intestinal type (72.9%). In surgery the majority of cases were found to be in T3 stage (87.5%). Her-2/Neu was positive in 10.4% of cases and it was negative in 89.6% of cases. Despite the higher rate of tumors with further expression of HER-2/Neu in those with a size over 5 cm and with vascular invasion, there was no significant association between Her-2/Neu and other variables (P > 0.05).
Conclusion: According to the results of this study, overexpression of HER-2/Neu in gastric cancer is low (10.4%) and there is no significant association with other variables. It is suggested that further similar studies with a larger sample size be carried out to definitely determine the association between this marker and prognostic factors.

Keywords

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2):87–108.
  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55(2):74-108.
  3. Malekzadeh R, Derakhshan MH, Malekzadeh Z. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med 2009; 12(6):576-83.
  4. Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol 2003; 56(1):1-9.
  5. Correa P. Helicobacter pylori and gastric cancer: state of the art. Cancer Epidemiol Biomarkers Prev 1996; 5(6):477-81.
  6. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for respectable gastroesophageal cancer. N Engl J Med 2006; 355(1):11-20.
  7. Lastraioli E, Raffaella Romoli M, Arcangeli A. Immunohistochemical biomarkers in gastric cancer research and management. International Journal of Surgical Oncology 2012; 2012: 868645.
  8. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366(1):2-16.
  9. Fornaro L, Lucchesi M, Caparello C, Vasile E, Caponi S, Ginocchi L, et al. Anti-HER agents in gastric cancer: from bench to bedside. Nat Rev Gastroenterol Hepatol 2011; 8(7):369-83.
  10. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 2008; 19(9):1523–9.
  11. 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; 33(10):2112-8.
  12. Giuffrè G, Ieni A, Barresi V, Caruso RA, Tuccari G. HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol 2012; 65(3):237-41.
  13. 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.
  14. Tan M, Yu D. Molecular mechanisms of erbB2-mediated breast cancer chemoresistance. Adv Exp Med Biol 2007; 608:119-29.
  15. Uchino S, Tsuda H, Maruyama K, Kinoshita T, Sasako M, Saito T, et al. Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer 1993; 72(11):3179-84.
  16. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 1999; 85(9):1894-902.
  17. Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol 2000; 18(11):2201-9.
  18. Ross JS, Mulcahy M. HER2 testing in gastric/gastroesophageal junction adenocarcinomas: unique features of a familiar test. Gastrointest Cancer Res 2011; 4(2):62-6.
  19. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine forHER2-positive advanced breast cancer. N Engl J Med 2006; 355(26):2733-43.
  20. Yan B, Yau EX, Bte Omar SS, Ong CW, Pang B, Yeoh KG, et al. A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol 2010; 63(9):839-42.
  21. Ananiev J, Gulubova M, Manolova I, Tchernev G. Prognostic significance of HER2/neu expression in gastric cancer. Wien Klin Wochenschr 2011; 123(13-14):450-4.
  22. Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-a systematic analysis of data from the literature. J Cancer 2012; 3:137-44.
  23. Liang JW, Zhang JJ, Zhang T, Zheng ZC. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumour Biol 2014; 35(5):4849-58.
  24. Gu J, Zheng L, Wang Y, Zhu M, Wang Q, Li X. Prognostic significance of HER2 expression based on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated meta-analysis. Tumour Biol 2014; 35(6):5315-21.
  25. Hadi AA, Hindawi AE, Hareedy A, Khalil H, Ashiry RA, Elia S, et al. Her2/neu protein expression and oncogene amplification in gastric carcinoma with clinico-pathological correlation in Egyptian patients. Open Access Maced J Med Sci 2016; 4(4):535-42.
  26. Seo KW, Jeon T, Kim S, Kim SS, Kim K, Suh BJ, et al. Epidemiologic study of human epidermal growth factor receptor 2 expression in advanced/metastatic gastric cancer: an assessment of human epidermal growth factor receptor 2 status in tumor tissue samples of gastric and gastro-esophageal junction cancer. J Gastric Cancer 2017; 17(1):52-62.
  27. Sreeram S, Chakraborti S, Naik R, Saha D, Radhakrishnan Y, Sridevi HB, et al. HER2 and helicobacter pylori status in resected gastric cancers: a pathological study of a gastroenterological issue. Journal of Clinical & Diagnostic Research 2017; 11(10):1-5.
  28. Zhu GJ, Xu CW, Fang MY, Zhang YP, Li Y. Detection of Her‑2/neu expression in gastric cancer: quantitative PCR versus immunohistochemistry. Exp Ther Med 2014; 8(5):1501-7.
  29. Lashkarizadeh MR, Bazrafshani MR, Izadi A, Hosseini F. Evaluation of HER2/neu gene amplification frequency in patients with gastric cancer using MLPA method. Journal of Torbat Heydariyeh University of Medical Sciences 2014; 2(4):38-45. [In Persian].
  30. Janbabaee G, Naghshvar F, Farazmandfar T, Salehi M, Rashidi M. Study of HER1, HER2 over expression in locally advanced gastric cancer and their correlation with overall survival. Journal of Mazandaran University of Medical Sciences 2012; 22(92):2-7. [In Persian].
  31. Gurel S, Dolar E, Yerci O, Samli B, Ozturk 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(2):74-8.
  32. Shi HZ, Wang YN, Huang XH, Zhang KC, Xi HQ, Cui JX, et al. Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer. World J Gastroenterol 2017; 23(10):1836-42.
  33. 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; 17(11):1501-6.
  34. 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. Br J Cancer 2009; 100(3):487-93.
  35. Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value–conclusions from 924 cases of two independent series. Cell Oncol 2010; 32(1-2):57-65.
  36. Emadian O, Naghshvar F, Torabizade ZH, Yaseri AR, Khalilian AR, Shahrbandian M. Determining the expression of p53 and HER2 with the related factors in prognosis of gastric carcinoma by immunohistochemistry. Journal of Mazandaran University of Medical Sciences 2011; 21(82):2-8. [In Persian].
  37. Oshima CT, Lanzoni VP, Iriya K, Forones NM. C-erbB-2 oncoprotein in gastriccarcinoma: correlation with clinical stage and prognosis. Int J Biol Markers 2000; 16(4):250-4.
  38. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005; 16(2):273-8.
  39. Xu CC, Yue L, Wei HJ, Zhao WW, Sui AH, Wang XM, et al. Significance of TFF3protein and Her-2/neu status in patients with gastric adenocarcinoma. Pathol Res Pract 2013; 209(8):479-85.
  40. Abbasi M, Mobaien A, Majlesi A, Kamalian N, Monsef A. A survey of p53 and HER-2/neu over expression in patients with gastric cancer and correlation with prognosis. Avicenna Journal of Clinical Medicine 2008; 15(3):5-10. [In Persian].
  41. Ognjenovic L, Trajkovski G, Gjoshev S, Shumkovski A, Dzambaz D, Hadzi-Manchev D, et al. HER2 positive gastric carcinomas and their clinico-pathological characteristics. Open Access Maced J Med Sci 2018; 6(7):1187-92.