RESUMEN
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.
Asunto(s)
Homólogo 1 de la Proteína MutL/biosíntesis , Proteína 2 Homóloga a MutS/biosíntesis , Receptor ErbB-2/biosíntesis , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Factores de Edad , Anciano , Vacuna BCG/uso terapéutico , Femenino , Humanos , Masculino , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Clasificación del Tumor , Pronóstico , Proto-Oncogenes Mas , Receptor ErbB-2/genética , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
Deregulated expression of inhibitors of apoptosis may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to chemo- and radiotherapy. In this study, we have investigated, by immunohistochemical technique, the expression and potential prognostic significance of survivin in a series of 49 clear cell type renal cell carcinoma (ccRCC). Survivin expression was significantly associated with poorly differentiated, advanced stages and more aggressive ccRCCs (p < 0.05). Patients with low survivin expression had statistically significant better survival rates than patients with high survivin expression (p < 0.05). This may be relevant for follow-up protocols design and/or alternative therapeutic approaches.
