Expression of Human Epidermal Growth Factor Receptor (Her 2/neu) and Proliferative Marker Ki-67: Association with Clinicopathological Parameters in Gallbladder Carcinoma.

PURPOSE: To evaluate the expression of Her2/neu and Ki-67 in benign and malignant gallbladder lesions, and to establish correlations with clinico-pathologic parameters.

MATERIALS AND METHODS: A retrospective analysis was conducted on formalin fixed paraffin embedded (FFPE) benign (n=25) and malignant gallbladder (n=25) tissue samples. Hematoxylin and eosin stained slides of each case were reviewed for: type of malignancy (whether adenocarcinoma, squamous cell carcinoma, or any other type); grade (well, moderate, and poor); depth of invasion; and pre-neoplastic changes in adjacent mucosal epithelium like metaplasia and dysplasia. Immunohistochemistry for Her 2 neu and Ki-67 was performed and data analysis was conducted using SPSS 17 software. Chi-square test was used to compare categorical/dichotomous variables. A P value of ≤0.05 was considered significant.

RESULTS: The difference of Her 2 neu expression and Ki67 index between benign and malignant groups was found to be statistically significant. Her2/neu positivity did not have any significant correlation with various clinicopathological parameters other than liver involvement. Five cases of gallbladder cancer showed both Her2/neu and Ki67 positivity. Ten cases were Ki67 positive but Her2/neu negative while one case was Her2/neu positive but Ki67 negative.

CONCLUSIONS: The present study demonstrated overexpression of Her2/neu and Ki67 in gallbladder cancer. A trend of decreasing Her2/neu expression with increasing grade of tumor was observed. Furthermore, greater Ki67 positivity was found in cases with lymph node metastasis and distant metastasis. Future studies with a larger number of patients will be required to precisely define the correlation of Her2/neu expression and Ki67 positivity with clinicopathological parameters. The results however are encouraging and suggest evaluation of Her2/neu as a candidate for targeted therapy.