The importance of acidic microenvironment in urothelial carcinomas of the bladder: relationship with carbonic anhydrase IX expression and prognostic factors

Aims: Bladder urothelial carcinoma (BUC) is a prevalent malignancy worldwide, ranking 13th in terms of mortality. Several prognostic factors affecting survival have been identified, including histologic grade, invasion of the muscularis propria, tumor diameter, and lymphovascular invasion. However, new markers that will be helpful in diagnosis, treatment and prognosis are still needed. Carbonic anhydrase IX (CA IX) is a tumor-associated cell surface glycoprotein that aids in adaptation to acidosis induced by hypoxia and plays a role in cancer progression.There are few studies on the prognostic impact of CA IX on BUCs. This study aimed to investigate whether CA IX is a promising diagnostic and prognostic biomarker in BUC. Methods: A retrospective analysis was conducted on 117 cases diagnosed with BUC whithout muscularis propria invasion between September 1995 and January 2023. Transurethral resection specimens were examined histological grade, lymphovascular invasion, tumor diameter by a single pathologist. CAIX was performed by immunohistochemical method. Results: Among the 117 patients included in the study, 61 had low-grade tumors, while the remaining 56 had high-grade tumors. CA IX expression exhibited a significant positive correlation with histological grade (p < 0.01), lymphovascular invasion (p < 0.01). and tumor diameter (p < 0.01). Low CA IX staining was observed in three normal tissues and ıt was found to be a biomarker in the distinction between malignant and benign cases. Conclusion: CA IX expression is associated with poor prognosis in BUCs as in some other tumors. Evaluation of CA IX staining may be important for patient follow-up and treatment strategies. Adding carbonic anhydrase enzyme inhibitors to chemotherapy regimens could potentially create new treatment options.