Background: Gallbladder cancer(GBC) is a very aggressive malignancy, diagnosed in advanced stage, with poor prognosis, and often difficult to treat with conventional modalities. Therefore, it necessitates exploring the molecular changes for developing an effective early diagnostic and therapeutic strategy. We aim to identify the expression of HER-2 and PD-L1 and their clinico-pathological associations in GBC patients.

Methodology: This was a prospective observational study performed in department of surgical gastroenterology of King George’s Medical Institute Lucknow on 68 patients of Gall bladder cancer proven by histopathological examination between November 2019 to November 2022. Immunohistochemical (IHC) detection for PD-L1 and HER-2/neu expression was performed on all the selected cases.

Results: The frequency of PD-L1 and HER 2/ neu over-expression was found 23.5% and 8.8% respectively in patients of GBC. The PD-L1 expression, at a cut off 1% and 10% was found positive in 14 (20.6%) and 2 (2.9%) patients respectively. The histological grade, nuclear grade, staging, and T staging were significantly associated with PD-L1 expression at a cut off 1% while at a cut off 10%, PD-L1 expression was significantly associated with histological type, diabetes mellitus, ascites, adjacent organ involvement, liver metastasis and TIL density. A significant association was found between HER 2 expression and lower histological grade, tumor marker CA 19-9 and nuclear grading.

Conclusion: HER2/neu expressions were observed in well differentiated tumour and in early stage of cancer. PD-L1 expression was observed more in moderately and poorly differentiated and in advanced stage GBC, it suggests that controlled clinical trials of PD-L1 targeted therapy can be conducted in patients with advanced gallbladder cancer. The present study evaluated somewhat lower but noteworthy proportion of HER-2 and PD-L1 positive GBC cases in which targeted therapy may improve the prognosis of patients.