Immunohistochemical Expression of HER2/neu, Ki-67 and MUC1 in Benign and Malignant Gall Bladder Lesions and its Association with Clinicopathological Parameters

Abstract

Introduction: Gall Bladder Carcinoma (GBC) is a diagnostic and a therapeutic challenge. Although it is increasing, chronic cholecystitis remains the most worldwide gall bladder lesions, harbouring many epithelial changes that may end in carcinoma. Aim: To investigate the expression of HER2/neu (Human Epidermal Growth Factor Receptor 2), Ki-67 and MUC1 (Mucin 1) in malignant and non-malignant gall bladder lesions, and to evaluate its relation with clinicopathologic parameters of GBC. Materials and Methods: This retrospective study included 40 cases of GBC, eight cases of gall bladder dysplasia, 10 cases of gall bladder metaplastic changes and 25 cases of chronic cholecystitis as a control group. The blocks were collected from the Department of Pathology of Benha University Hospital, from January 2012 to December 2019. Immunohistochemical staining results of HER2/neu, Ki-67 and MUC1 were analysed and correlated by Statistical Package for the Social Sciences (SPSS) version 16 and Chi-square test or Fisher’s-exact tests. Results: Positive HER2/neu expression (+2, +3) was detected in 47.5% (19/40) of malignant cases and 12.5% (1/8) of dyspastic group, at the same time it was completely absent in the metaplastic and cholecystitis cases (p<0.01). Similarly, Ki-67 Labeling Index (LI) (≥20%) expression was found in 55% (22/40) of malignant group, while it was completely absent in the other three studied groups. All cases of malignant group 100% (40/40), 50% (4/8) of dysplastic one, one case of metaplastic (1/10) showed cytoplasmic expression of MUC1, at the same time it was completely absent in control group (0/25) (p<0.01). High MUC1 expression was found in 75% of both malignant (30/40) and dysplastic (6/8) studied cases and only one case (10%) of metaplastic group (p<0.01). There was a significant correlation between MUC1 expression and studied parameters of GBC. Conclusion: HER2/neu, and Ki-67 are overexpressed in GBC cases compared with control and dysplastic group. The study also highlights that MUC1 would be a better marker of malignant transformation of gall bladder epithelium and its depolarised expression would be reliable for detection of invasive carcinoma, so a new therapeutic agent can target these cell surface adhesion molecule (MUC1). HER2/neu can be considered as a candidate for targeted therapy in GBC treatment strategy.