Immunohistochemical Expression of Novel Therapeutic Targets in Squamous Cell Carcinoma of the Bladder

Squamous cell carcinoma (SCC) of the bladder is an aggressive histologic subtype with distinct clinical behavior and limited treatment options after platinum-based chemotherapy. This study aimed to evaluate potential therapeutic targets in bladder SCC.

A retrospective cohort of 790 patients who underwent radical cystectomy for bladder cancer between 2011 and 2021 was screened to identify cases with histologically confirmed SCC. All SCC cases in the pathology department from 2003 to 2011 were also reviewed. Clinical and pathological data from 54 patients were analyzed. A tissue microarray (TMA) was constructed, and immunohistochemical (IHC) analyses were performed for programmed death-ligand 1 (PD-L1), nectin cell adhesion molecule 4 (NECTIN4), trophoblast cell-surface antigen 2 (TROP2), human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), and CD8⁺ T cells. Expression levels were assessed for prognostic relevance using the log-rank test and Kaplan-Meier survival analysis.

A TMA comprising samples from 42 of 54 patients (22 pure SCC, 20 partial SCC) was successfully constructed. NECTIN4 (positive vs. negative) expression, PD-L1 (combined positive score ≥ 10 vs. <10) expression, and CD8⁺ density (high vs. low) showed a nearly equal distribution across the cohort. HER2 expression was detected in 14.3% of cases, CEACAM5 in 21.4%, and TROP2 in 83.3% of tumors. High NECTIN4 expression, increased CD8⁺ density, and administration of adjuvant chemotherapy were associated with improved overall survival.

Several actionable targets were identified in bladder SCC, supporting further exploration of targeted therapies.