Immunohistochemical Evaluation of Apoptosis and Multidrug Resistance- Related Markers in Gallbladder Dysplasia and Carcinoma

Abstract

Objective: The search for treatment success in gallbladder carcinomas, which is one of the tumors with the most aggressive course, poor prognosis, and tendency to show resistance to treatment, continues today. Treatments targeting pathways related to genetic changes de- tected in most solid tumors offer new hope in the treatment of these tumors. Some of these treatment modalities target apoptosis-related pathways, and mammalian target of rapamycin (mTOR), p38, Bcl-2, and caspase-3 are important components of this pathway. Methods: In the study, mTOR, caspase-3, p38, Bcl-2, LL-37, MDR1, multidrug resistance protein (MRP)1, MRP6, and MRP7 immunohistochemical staining were applied to paraffin blocks of 27 gallbladder cancer and 62 cases with gallbladder dysplasia. The immunohisto- chemically stained sections were evaluated and scored. Results: mTOR, p38, and caspase-3 expressions were found to be significantly increased in dysplasia and tumor groups, and in dysplastic and malignant cells. While there was no signifi- cant difference in the expression of MRP1 and MRP7, MRP6 was significantly overexpressed. Conclusion: In this study, increased expression of mTOR, p38, and caspase-3 in the dys- plastic and malignant cells of the gallbladder may show that it has a role in the carcinogenesis process in the gallbladder. The study also shows that MRP6 may also play a role in the devel- opment of drug resistance in gallbladder carcinoma.