Ulrich Krafft1, Stephan Tschirdewahn1, Jochen Hess1, Nina N Harke1, Boris Hadaschik1, Csilla Olah1, Susanne Krege2, Peter Nyirády3, Attila Szendröi3, Miklós Szücs3, Orsolya Módos3, Eszter Székely4, Henning Reis5, Tibor Szarvas6. 1. Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 2. Department of Urology, Pediatric Urology and Urologic Oncology, Kliniken Essen-Mitte, Essen, Germany. 3. Department of Urology, Semmelweis University, Budapest, Hungary. 4. Second Department of Pathology, Semmelweis University, Budapest, Hungary. 5. Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 6. Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany; Department of Urology, Semmelweis University, Budapest, Hungary. Electronic address: sztibusz@gmail.com.
Abstract
OBJECTIVES: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. METHODS: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. RESULTS: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. CONCLUSIONS: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.
OBJECTIVES:Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. METHODS:Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. RESULTS: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. CONCLUSIONS: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.
Authors: Olga Méndez; José Pérez; Jesus Soberino; Fabricio Racca; Javier Cortés; Josep Villanueva Journal: Int J Mol Sci Date: 2019-11-26 Impact factor: 5.923
Authors: Behzad Mansoori; Ali Mohammadi; Henrik J Ditzel; Pascal H G Duijf; Vahid Khaze; Morten F Gjerstorff; Behzad Baradaran Journal: Genes (Basel) Date: 2021-02-13 Impact factor: 4.096
Authors: Michael Wessolly; Fabian D Mairinger; Thomas Herold; Boris Hadaschik; Tibor Szarvas; Henning Reis Journal: Genes (Basel) Date: 2022-02-25 Impact factor: 4.096