CC BY-NC-ND 4.0 · South Asian J Cancer 2023; 12(02): 135-140
DOI: 10.1055/s-0042-1759601
Original Article
Gastrointestinal Cancer

Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India

Abhilash V. B.
1   ESIC Hospital, Varanasi, Uttar Pradesh, India
,
Manas Kumar Behera
2   Department of Hepatology, Srirama Chandra Bhanja (SCB) Medical College, Bhubaneswar, Odisha, India
,
Shashikant C. U. Patne
3   Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
,
Sunit Kumar Shukla
4   Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
,
Vinod Kumar Dixit
4   Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
› Author Affiliations

Abstract

Zoom Image
Manas Kumar Behera

Background and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease.

Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done.

Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61–3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan–Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression (p = 0.001).

Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.



Publication History

Article published online:
02 March 2023

© 2023. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol 2019; 14 (01) 26-38
  • 2 Rao DN, Ganesh B. Estimate of cancer incidence in India in 1991. Indian J Cancer 1998; 35 (01) 10-18
  • 3 Sharma A, Radhakrishnan V. Gastric cancer in India. Indian J Med Paediatr Oncol 2011; 32 (01) 12-16
  • 4 Mohandas KM, Jagannath P. Epidemiology of digestive tract cancers in India. VI. Projected burden in the new millennium and the need for primary prevention. Indian J Gastroenterol 2000; 19 (02) 74-78
  • 5 Dikshit RP, Mathur G, Mhatre S, Yeole BB. Epidemiological review of gastric cancer in India. Indian J Med Paediatr Oncol 2011; 32 (01) 3-11
  • 6 Pavithran K, Doval DC, Pandey KK. Gastric cancer in India. Gastric Cancer 2002; 5 (04) 240-243
  • 7 Malhotra SL. Geographical distribution of gastrointestinal cancers in India with special reference to causation. Gut 1967; 8 (04) 361-372
  • 8 Yan SY, Hu Y, Fan JG. et al. Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World J Gastroenterol 2011; 17 (11) 1501-1506
  • 9 Sukanya JS, Raj PV, Thanka J. Role of HER2neu expression in gastric cancer. Indian J Pathol Microbiol 2021; 64 (01) 58-64
  • 10 Lastraioli E, Romoli MR, Arcangeli A. Immunohistochemical biomarkers in gastric cancer research and management. Int J Surg Oncol 2012; 2012: 868645
  • 11 Bang YJ, Van Cutsem E, Feyereislova A. et al; ToGA Trial Investigators. 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 (9742): 687-697
  • 12 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 (07) 797-805
  • 13 Behera MK, Swain SN, Sahu MK. et al. Diastolic dysfunction is a predictor of poor survival in patients with decompensated cir-rhosis. Int J Hepatol 2021; 2021: 5592376
  • 14 GBD 2017 Stomach Cancer Collaborators. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol 2020; 5 (01) 42-54
  • 15 Roy PS, Nyodu T, Hazarika M. et al. Prevalence of HER2 expression and its correlation with clinicopathological parameters in gastric or gastroesophageal junction adenocarcinoma in North-East Indian population. Asian Pac J Cancer Prev 2019; 20 (04) 1139-1145
  • 16 Ishida T, Tsujisaki M, Hanzawa Y. et al. Significance of erbB-2 gene product as a target molecule for cancer therapy. Scand J Immunol 1994; 39 (05) 459-466
  • 17 Tokunaga A, Onda M, Okuda T. et al. Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer. Cancer 1995; 75 (6, suppl): 1418-1425
  • 18 Tanner M, Hollmén M, Junttila TT. et 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 (02) 273-278
  • 19 Gordon MA, Gundacker HM, Benedetti J. et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 2013; 24 (07) 1754-1761
  • 20 Park DI, Yun JW, Park JH. et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006; 51 (08) 1371-1379
  • 21 Sekaran A, Kandagaddala RS, Darisetty S. et al. HER2 expression in gastric cancer in Indian population—an immunohistochemistry and fluorescence in situ hybridization study. Indian J Gastroenterol 2012; 31 (03) 106-110
  • 22 He C, Bian XY, Ni XZ. et al. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer. World J Gastroenterol 2013; 19 (14) 2171-2178
  • 23 Uchino S, Tsuda H, Maruyama K. et al. Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer 1993; 72 (11) 3179-3184
  • 24 Hilton DA, West KP. c-erbB-2 oncogene product expression and prognosis in gastric carcinoma. J Clin Pathol 1992; 45 (05) 454-456
  • 25 Jaehne J, Urmacher C, Thaler HT, Friedlander-Klar H, Cordon-Cardo C, Meyer HJ. Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma. J Cancer Res Clin Oncol 1992; 118 (06) 474-479
  • 26 Ananiev J, Gulubova M, Manolova I, Tchernev G. Prognostic significance of HER2/neu expression in gastric cancer. Wien Klin Wochenschr 2011; 123 (13-14): 450-454
  • 27 Zhang XL, Yang YS, Xu DP. et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 2009; 33 (10) 2112-2118
  • 28 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) 1331-1339
  • 29 Xie SD, Xu CY, Shen JG, Jiang ZN, Shen JY, Wang LB. HER 2/neu protein expression in gastric cancer is associated with poor survival. Mol Med Rep 2009; 2 (06) 943-946
  • 30 Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 2008; 19 (09) 1523-1529