Role of Epidermal Growth Factor Receptor in Gallbladder Carcinoma and its Association with Various Clinicopathological Parameters: A Cross-sectional Study

Abstract

Introduction: Carcinoma of gallbladder is an aggressive disease with poor outcome. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor that regulate growth, proliferation and differentiation in cells. Increased EGFR receptor expression has been studied in various cancers like lung, colorectal, breast and pancreatic tumours and anti-EGFR antibody has been used successfully for therapeutic and diagnostic purposes. Aim: To evaluate EGFR expression in gallbladder carcinoma and its association with clinicopathological factors to reveal its relation to prognosis. Materials and Methods: This cross-sectional retrospective observational study in which 64 samples were collected of resected specimen of Gallbladder Carcinoma (GBC), from the Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh, India, between March 2017 to September 2018. Haematoxylin and Eosin (H&E) stained sections were evaluated for tumour type and histopathological grading and TNM staging was done. Immunohistochemistry (IHC) was performed and analysed prospectively using ready to use anti-EGFR as per manufacturer’s protocols. Association between EGFR expression and clinicopathological factors were statistically analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Results: The EGFR expression was positive in 52 (81.25%) cases of GBC which showed a highly significant association between tumour grade and stage. About 60% of poorly differentiated GBC displayed strong (3+) staining intensity as compared to 30% of moderately differentiated (3+) and 10% of well differentiated tumours (3+). It suggests that with decreasing differentiation of tumour EGFR staining intensity increases (p<0.001). Positivity rate of EGFR expression were also increased with increase of tumour TNM stage (stage I to stage IV). Strong EGFR expression was associated with decreased overall survival with significant p value (p=0.031, log rank test). Conclusion: The EGFR expression is inversely related with tumour differentiation, and overall survival. EGFR expression increases with high TNM staging. So, it can be used as prognostic marker for gallbladder carcinoma and opening a hope towards the new therapeutic options.

Keywords

• adenocarcinoma
• gallbladder cancer
• immunohistochemistry
• prognostic marker