You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2016MP45-12 PROGNOSTIC VALUE OF DNA DAMAGE RESPONSE RELATED PROTEINS IN NON-MUSCLE INVASIVE BLADDER CANCER Albert Frances, Nuria Juanpere, Judith Penafiel, Gloria Nohales, Cristina Camara, Alex Garcia-Larrosa, Jose Maria Abascal, Joan Vila, Josep Lloreta, and Lluis Cecchini Albert FrancesAlbert Frances More articles by this author , Nuria JuanpereNuria Juanpere More articles by this author , Judith PenafielJudith Penafiel More articles by this author , Gloria NohalesGloria Nohales More articles by this author , Cristina CamaraCristina Camara More articles by this author , Alex Garcia-LarrosaAlex Garcia-Larrosa More articles by this author , Jose Maria AbascalJose Maria Abascal More articles by this author , Joan VilaJoan Vila More articles by this author , Josep LloretaJosep Lloreta More articles by this author , and Lluis CecchiniLluis Cecchini More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.289AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Non muscle-invasive bladder cancer (NMIBC) is characterized by a high risk of recurrence after transurethral resection (Five-year recurrence rate is 31-78%). Several biomarkers have been studied as a recurrence prognostic tool, being p53 the most widely investigated. P53 is a tumor suppressor that plays an important role in DNA damage response (DDR), being up regulated by a network of proteins such as ATM or Chk2 and their activated forms (phosphorylated). The aim of our study is to investigate the possible role of DNA damage response (DDR) related proteins in the recurrence of NMBIC. METHODS We performed a retrospective study of 172 consecutive patients (median age 69 years, 84% males) with primary NMIBC diagnosis within the period 1998-2003. Representative paraffin blocks from each patient were used to construct three TMA. Immunohistochemistry (IHC) staining for ATM, Chk-2, p53 and their active forms (phosphorylated) was performed. IHC results were analyzed in a qualitative and a semi-quantitative manner (histoscore). Hazard ratios (HR) were calculated using Cox proportional Hazards model. RESULTS With a median follow up of 72 months, the rate of recurrence was 50.6%. Median time to first recurrence was 16.2 months. We observed a higher risk of recurrence in patients who expressed pATM (HR 2, 54, IC 95% 1.02-6.29) and p53 (HR 1.66, IC 95% 1.02-2,68). If we subdivide patients according to grade and tumor stage, we found that pTa tumors with pATM expression had 8.24 times more possibilities to recur than those which did not expressed it (IC 95% 1.14-59.6). In multivariate analysis, pATM expression was an independent predictor for recurrence in pTa tumors (HR 8.41, IC 95% 1.16-60.9). We did not find any relation between recurrence and expression of Chk2, pCh2 or ATM. In Cox proportional Hazards model, using the p53 cut point of 11(which corresponds to p53 median value), recurrence risk of pTa with p53 ≥ 11 and expression of pATM was 34.3%, 68.4% and 86.5% in 1, 2 and 5 years respectively, whereas recurrence risk of pTa tumors with p53<11 and negative expression of pATM was 2.22%, 5.95% and 10.17% in 1, 2 and 5 years. CONCLUSIONS The positive expression of p53 and pATM increases the risk of recurrence in NMIBC patients. The risk of recurrence is clearly increased in pTa tumors when positive staining of pATM is present, especially if there is also an overexpression of p53. Further studies are needed to corroborate the prognostic value of pATM expression in recurrence of NMIBC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e612-e613 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Albert Frances More articles by this author Nuria Juanpere More articles by this author Judith Penafiel More articles by this author Gloria Nohales More articles by this author Cristina Camara More articles by this author Alex Garcia-Larrosa More articles by this author Jose Maria Abascal More articles by this author Joan Vila More articles by this author Josep Lloreta More articles by this author Lluis Cecchini More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...