Clinicopathologic and Prognostic Significance of Her2 Neu and p53 Overexpression in Gastric Adenocarcinoma

Swathi Raj; Hazeena C; Deepak Lavatt; E V Gopi; Suprya N K; Swathy Shanker

doi:10.21276/apalm.3594

Authors

Swathi Raj Department of Pathology, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, Kerala, India
Hazeena C Department of Pathology, Government Medical College, Calicut, Kerala, India
Deepak Lavatt Department of Pathology, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, Kerala, India
E V Gopi Department of Surgery, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, Kerala, India
Suprya N K Department of Pathology, Government Medical College, Calicut, Kerala, India
Swathy Shanker Department of Pathology, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, Kerala, India

DOI:

https://doi.org/10.21276/apalm.3594

Keywords:

gastric adenocarcinoma, P53, Her2/neu

Abstract

Background: Gastric cancer is one of the major causes of mortality worldwide. Human epidermal growth factor receptor 2 is a protooncogene present on chromosome 17. Genetic alternations play a pivotal role in the pathogenesis of cancers involving carcinoma of stomach. The most frequent change is observed in p53 gene. The objective of this study is to determine the percentage of expression of Her2 Neu and p53 nuclear protein in gastric adenocarcinoma and compare the expression with other clinicopathological variables.

Methods: In this cross-sectional observational study, 90 cases of gastric adenocarcinoma in the time period of 3 years were taken. Scoring for Her2 Neu and p53 expression was done using specific scoring systems for all the cases. Data were entered in Microsoft Excel and analysed using SPSS software.

Results: In our analysis, majority of patients were distributed in the 61-70 age group (37.8%). Male to Female ratio was 2.56. Out of 90 cases, 71.7% was intestinal type of adenocarcinoma. p53 expression was seen in 44.4% of gastric adenocarcinomas and intestinal type cases showed increased expression, while Her2 Neu expression was seen in 11 cases and all the cases were of intestinal type. In this study, statistically significant association was found between p53 expression and lymph node involvement in the tumour and also between p53 expression and serosal invasion of the tumour. No statistically significant association was found between Her2 Neu overexpression and other variables.

Conclusion: p53 expression correlates with poor prognosis of the patients as it is more frequently associated with cases showing lymph node metastasis and increased depth of invasion of tumour. p53 expression was also frequent among higher grade tumours which also indicate the poor prognostic value of this marker. Targeted therapy with anti-Her2 Neu antibody can be implemented in the cases with Her2 Neu overexpression.

References

1. Wild CP, Weiderpass E, Stewart BW. World Cancer Report 2019. International Agency for Research on Cancer; Lyon, France: 2019.

2. Hajdu SI. A note from history: Landmarks in history of cancer, part 1. Cancer. 2011;117:1097-1102.

3. Santoro E. The history of gastric cancer: Legends and chronicles. Gastric Cancer. 2005:8:71-74.

4. Alberts SR, Cervantes A, van de Velde CJ. Gastric cancer: Epidemiology, pathology and treatment. Ann Oncol. 2003;14:ii31-6.

5. Joypaul BV, Hopwood D, Newman EL et al. The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. Br J Cancer. 1994; 69: 943.

6. Hurlimann J, Saraga EP. Expression of p53 protein in gastric carcinomas. Am J Surg Pathol. 1994; 18: 1247.

7. Hynes N, Stern D. The biology of erbB-2/Neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994; 1198:165-184.

8. Mushtaq S, et al. Epidemiological trends and patterns of gastric cancer in the Kashmir Valley, India. Clin Epidemiol Glob Health. 2022:34:102057.

9. Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I, Al-Nabhani M, et al. The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol. 2005;91:243-52.

10. Tzanakis NE, Peros G, Karakitsos P, Giannopoulos GA, Efstathiou SP, Rallis G, et al. Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients. Acta Chir Belg. 2009;109:606-11.

11. Petersson F, Borch K, Franzen LE. Gastric epithelial proliferation and p53 and p21 expression in a general population sample: relations to age, sex, and mucosal changes associated with H. pylori infection. Dig Dis Sci. 2002:47:1558-66.

12. Jung SU, et al. Clinicopathological correlations with p53 expression in gastric cancer patients with curative resection. Korean J Clin Oncol. 2014;10(1):12-17.

13. Goncalves AR, Carneiro AJ, Martins I, de Faria PA, Ferreira MA, de Mello EL, et al. Prognostic significance of p53 protein expression in early gastric cancer. Pathol Oncol Res. 2011 17:349-55.

14. Lazăr D, Taban S, Sporea I, Dema A, Cornianu M, Lazăr E, Goldiş A, Raţiu I, Vernic C. The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients. Rom J Morphol Embryol. 2010;51(2):249-57.

15. Tanner M, Hollmen M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase Ila gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005:16:273-278.

16. Gravalos C, Jimeno A. Her2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523-1529.

17. Mizutani T. Onda M, Tokunaga A, et al. Relationship of c-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer. Cancer. 1993;72:2083-2088.