A female with asymptomatic primary biliary cirrhosis associated with pernicious anemia.

BACKGROUND

Gallbladder adenocarcinoma has limited global prevalence but occurs more frequently in certain regions. The disease is often diagnosed at advanced stages, restricting therapeutic options and contributing to poor outcomes. The molecular mechanisms underlying its development remain largely undefined, complicating the discovery of targeted therapies. Microsatellite instability (MSI), resulting from defective DNA mismatch repair, plays a well-established role in several malignancies; however, its significance in gallbladder adenocarcinoma remains unclear. Characterizing MSI status may help identify patients eligible for novel therapeutic approaches. This study investigates the loss of DNA mismatch repair protein expression in gallbladder adenocarcinoma.

METHODS

Samples diagnosed as gallbladder adenocarcinoma were assessed for the expression of four DNA mismatch repair proteins using immunohistochemistry. Antibodies against MLH1, MSH2, PMS2, and MSH6 were employed to evaluate protein expression status. The study included 109 cases, both prospective and retrospective. Cases were included if sufficient paraffin-embedded tissue and relevant clinical data were available. Protein expression results were analysed in relation to clinical parameters and tumor-infiltrating lymphocytes.

RESULTS

The majority of patients were female. Radical cholecystectomy was the most common surgical procedure, while incidentally detected cases were typically managed with laparoscopic cholecystectomy. Most tumors demonstrated moderate differentiation. Immunohistochemistry revealed intact protein expression in 64 cases, whereas 45 cases showed loss of at least one mismatch repair protein. Loss of mismatch repair protein expression was significantly associated with the presence of tumor-infiltrating lymphocytes but not with other clinicopathological features.

CONCLUSION

Although still incompletely defined, MSI may represent a biologically and clinically relevant subset of gallbladder adenocarcinoma. Clarifying its role could help identify patients who may benefit from targeted or immunotherapy-based treatment strategies. Larger multicenter studies with standardized methodologies are warranted to establish the prevalence, prognostic value, and therapeutic implications of MSI in gallbladder adenocarcinoma.