Francesca Sanguedolce1, Antonella Cormio2, Paolo Massenio3, Maria C Pedicillo1, Simona Cagiano1, Francesca Fortunato4, Beppe Calò3, Giuseppe Di Fino3, Giuseppe Carrieri3, Pantaleo Bufo1, Luigi Cormio5. 1. Department of Pathology, University of Foggia, Viale L. Pinto 1, 71122, Foggia, FG, Italy. 2. Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70124, Bari, BA, Italy. 3. Department of Urology, University of Foggia, Viale L. Pinto 1, 71122, Foggia, FG, Italy. 4. Department of Epidemiology and Public Health, University of Foggia, Viale L. Pinto 1, 71122, Foggia, FG, Italy. 5. Department of Urology, University of Foggia, Viale L. Pinto 1, 71122, Foggia, FG, Italy. luigicormio@libero.it.
Abstract
PURPOSE: The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). RESULTS: HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. CONCLUSIONS: Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.
PURPOSE: The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). RESULTS:HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. CONCLUSIONS: Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.
Authors: Francesca Sanguedolce; Magda Zanelli; Andrea Palicelli; Stefano Ascani; Maurizio Zizzo; Giorgia Cocco; Lars Björnebo; Anna Lantz; Ugo Giovanni Falagario; Luigi Cormio; Giuseppe Carrieri Journal: Int J Mol Sci Date: 2022-07-15 Impact factor: 6.208
Authors: B Calò; F Sanguedolce; F Fortunato; G Stallone; N d'Altilia; M Chirico; U Falagario; Vito Mancini; G Carrieri; L Cormio Journal: Medicine (Baltimore) Date: 2019-08 Impact factor: 1.817
Authors: Beppe Calò; Francesca Sanguedolce; Ugo G Falagario; Marco Chirico; Francesca Fortunato; Emanuel Carvalho-Diaz; Gian Maria Busetto; Carlo Bettocchi; Giuseppe Carrieri; Luigi Cormio Journal: World J Urol Date: 2021-04-08 Impact factor: 4.226