Prognostic Significance of Her-2/Neu and Ki-67 Expression in Gallbladder Carcinoma: A Clinicopathological Study...

Background Gallbladder carcinomas (GBC) are aggressive biliary tract malignancies, which, as a result of advanced stage at presentation and poor outcome with standard treatment, lead to significant mortality. There is an unmet need to find prognostic and predictive biomarkers in GBC that can guide treatment escalation. Hence, we aimed to study the expression of Her-2/Neu and Ki-67 by immunohistochemistry (IHC) in GBC and their correlation with clinicopathological parameters and survival outcomes. Method This retrospective study was conducted at a tertiary cancer center in North India over a period of 20 months, during which GBC cases were retrieved, and IHC for Her-2/Neu and Ki-67 was performed and analyzed. Result A total of 133 cases of GBC were analyzed, with a median age of 54.1 years, comprising 93 females (70%). Adenocarcinomas were the most common histology with 125 cases (94%), and most cases (n=54, 40.6%) were moderately differentiated. Positive Her-2/Neu expression was found in 30 cases (22.6%), with a significant loss of Her-2/Neu expression as tumor grade increased (p-value <0.05). The Ki-67 proliferation index showed a significant association with increasing tumor grade (p-value <0.05). A significant correlation was noted between higher tumor grades 2/3 and metastatic/inoperable disease, liver, and lymph node metastasis (p-value <0.05). Median overall survival (OS) was 6 months in resectable and three months in metastatic disease. However, no significant association was noted between OS and Her-2/Neu positivity, grade, or Ki-67 in metastatic/inoperable disease. In resectable GBC, median OS was significantly better in grade 1 cancers than in higher-grade 2/3 cancers by 12 months (p-value <0.05), whereas a trend towards better OS was seen in cancers with Ki-67 less than 50. Her-2/Neu positivity made no difference in OS for resectable cancers. Conclusion Her-2/Neu positivity declines with poor tumor differentiation, without any effect on prognosis in resectable GBC. The Ki67 index, along with tumor grading, offers potential as a predictive and prognostic marker in resectable GBC.