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Immunohistochemical Expression of Novel Therapeutic Targets in Squamous Cell Carcinoma of the Bladder
Lisa J Frey1, Nina Lache1, Nikita D Fischer1
1Department of Urology and Pediatric Urology, Mainz University Medical Center, Langenbeckstraße 1, Mainz, Germany.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusion:
Several actionable targets were identified in bladder SCC, supporting further exploration of targeted therapies.
Insights
This study identified potential therapeutic targets for bladder squamous cell carcinoma (SCC). High NECTIN4 expression and increased CD8+ T cell density were linked to better survival in bladder SCC patients.
Area of Science:
- Oncology
- Urologic Oncology
- Cancer Research
Background:
- Bladder squamous cell carcinoma (SCC) is an aggressive subtype with limited treatment options.
- Platinum-based chemotherapy is often ineffective for advanced bladder SCC.
Purpose of the Study:
- To evaluate potential therapeutic targets in bladder SCC.
- To identify biomarkers associated with prognosis in bladder SCC.
Main Methods:
- Retrospective analysis of 54 bladder SCC cases.
- Tissue microarray (TMA) construction and immunohistochemical (IHC) analysis for PD-L1, NECTIN4, TROP2, HER2, CEACAM5, and CD8+ T cells.
- Survival analysis using log-rank test and Kaplan-Meier curves.
Main Results:
- NECTIN4, PD-L1, and CD8+ T cell expression varied across the cohort.
- HER2, CEACAM5, and TROP2 were detected in a subset of tumors.
- High NECTIN4 expression, increased CD8+ T cell density, and adjuvant chemotherapy correlated with improved overall survival.
Conclusions:
- Identification of actionable therapeutic targets in bladder SCC.
- Supports further investigation of targeted therapies for bladder SCC.
