Almudena Zapatero1, Manuel Morente2, Santiago Nieto3, Carmen Martín de Vidales4, Consuelo Lopez5, Magdalena Adrados5, Ramón Arellano6, Maria Jesus Artiga2, Feliciano Garcia-Vicente4, Luis Miguel Herranz7, Olwen Leaman4. 1. Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain. Electronic address: almudena.zapatero@salud.madrid.org. 2. Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 3. Department of Pathology, University Hospital Henares, Madrid, Spain. 4. Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain. 5. Department of Pathology, La Princesa University Hospital, Madrid, Spain. 6. Department of Urology, La Princesa University Hospital, Madrid, Spain. 7. Department of Urology, University Hospital Henares, Madrid, Spain.
Abstract
PURPOSE: The present study analyzed the expression by immunochemistry of the novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit (PSMB4) in men with localized prostate cancer (PC) who were treated with dose-escalation radiotherapy (RT) and androgen deprivation therapy. MATERIALS AND METHODS: Between 1996 and 2004, a cohort of 129 patients with PC who underwent diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled in this study. Suitable archival diagnostic tissue was obtained from 89 patients. Median follow-up was 129 months (48-198). Correlation analysis was done to assess association between PAK6 and PSMB4 expression and clinical outcome. RESULTS: PAK6 and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04) correlated with higher Gleason scores. In the multivariate analysis, the intensity of PSMB4 staining was an independent predictor of local relapse (hazard ratio = 8.6, P = 0.04). CONCLUSIONS: To our knowledge, this is the first description of PAK6 and PSMB4 expression in the diagnostic specimens of men with PC who were treated with RT. If confirmed by further studies, increased expression of these genes could be used to identify patients at a high risk of developing local failure following high-dose RT, thus better tailoring treatments for the individual patient.
PURPOSE: The present study analyzed the expression by immunochemistry of the novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit (PSMB4) in men with localized prostate cancer (PC) who were treated with dose-escalation radiotherapy (RT) and androgen deprivation therapy. MATERIALS AND METHODS: Between 1996 and 2004, a cohort of 129 patients with PC who underwent diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled in this study. Suitable archival diagnostic tissue was obtained from 89 patients. Median follow-up was 129 months (48-198). Correlation analysis was done to assess association between PAK6 and PSMB4 expression and clinical outcome. RESULTS:PAK6 and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04) correlated with higher Gleason scores. In the multivariate analysis, the intensity of PSMB4 staining was an independent predictor of local relapse (hazard ratio = 8.6, P = 0.04). CONCLUSIONS: To our knowledge, this is the first description of PAK6 and PSMB4 expression in the diagnostic specimens of men with PC who were treated with RT. If confirmed by further studies, increased expression of these genes could be used to identify patients at a high risk of developing local failure following high-dose RT, thus better tailoring treatments for the individual patient.
Authors: A Zapatero; M Adrados; L Torres; M S Talaya; A Cruz Conde; C Martin de Vidales; L Vega Piris; C Olivier; M T Murillo Journal: Rep Pract Oncol Radiother Date: 2019-12-09