MP50-16 A PANEL OF TISSUE BIOMARKERS EXPRESSION TO ENHANCE PROGNOSTIC STRATIFICATION IN LOCALLY-ADVANCED AND METASTATIC UROTHELIAL CANCERS (UC) UNDERGOING PERI-OPERATIVE AND FIRST-LINE PLATINUM-BASED CHEMOTHERAPY.

You have accessJournal of UrologyBladder Cancer: Natural History & Pathophysiology1 Apr 2014MP50-16 A PANEL OF TISSUE BIOMARKERS EXPRESSION TO ENHANCE PROGNOSTIC STRATIFICATION IN LOCALLY-ADVANCED AND METASTATIC UROTHELIAL CANCERS (UC) UNDERGOING PERI-OPERATIVE AND FIRST-LINE PLATINUM-BASED CHEMOTHERAPY. Andrea Necchi, Patrizia Giannatempo, Biagio Paolini, Luigi Mariani, Elena Farè, Daniele Raggi, Nicola Nicolai, Luigi Piva, Mario Catanzaro, Davide Biasoni, Tullio Torelli, Silvia Stagni, Massimo Maffezzini, Alessandro Gianni, Maurizio Colecchia, and Roberto Salvioni Andrea NecchiAndrea Necchi More articles by this author , Patrizia GiannatempoPatrizia Giannatempo More articles by this author , Biagio PaoliniBiagio Paolini More articles by this author , Luigi MarianiLuigi Mariani More articles by this author , Elena FarèElena Farè More articles by this author , Daniele RaggiDaniele Raggi More articles by this author , Nicola NicolaiNicola Nicolai More articles by this author , Luigi PivaLuigi Piva More articles by this author , Mario CatanzaroMario Catanzaro More articles by this author , Davide BiasoniDavide Biasoni More articles by this author , Tullio TorelliTullio Torelli More articles by this author , Silvia StagniSilvia Stagni More articles by this author , Massimo MaffezziniMassimo Maffezzini More articles by this author , Alessandro GianniAlessandro Gianni More articles by this author , Maurizio ColecchiaMaurizio Colecchia More articles by this author , and Roberto SalvioniRoberto Salvioni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1137AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Information on the prognostic role of druggable pathways for selection and treatment of patients (pts) is needed. A systematic evaluation of biomarker expression has been commenced at our tertiary cancer center and here we report on the early results. Methods Samples from primary tumor and/or metastases were evaluated for expression of a panel of biomarkers (BMKs) by immunohistochemistry (IHC) including: ERCC1, EGFR, HER2/neu, VEGFR, PDGFR, p53, p63, cKIT, PTEN. Two cohorts were selected: pts with locally advanced (T2-4±N+M0) UC receiving peri-operative cisplatin-based chemotherapy (CT) (cohort 1) and metastatic pts receiving first-line platinum-based CT (cohort 2). IHC results were assessed according to standard protocols and dichotomized as positive (≥1+) or negative for all markers. Tumor was deparaffinized and specific antigen retrieval determined for individual antibodies. Fisher exact test was used to evaluate the association with response for pts with measurable disease. Cox regression model analyzed staining results with PFS and OS in uni/multivariable analysis (UVA/MVA), adjusted for prognostic variables (lymph-node status [cohort 1], Bajorin score [cohort 2]). Results From 03/2000 to 03/2013, 86 cases were retrieved (N=30 in cohort 1 and N=56 in cohort 2). Rates of staining positivity were: 37/63 (59%) ERCC1, 34/50 (68%) EGFR, 41/53 (77%) HER2/neu, 45/62 (72%) VEGFR, 11/56 (18%) PDGFR, 26/48 (54%) p53, 41/48 (85%) p63, 9/47 (19%) cKIT, and 11/38 (29%) PTEN. BMKs were uniformly distributed (p always >0.05) and no association between staining and response was found in assessable pts. Median follow-up was 29.5 mos (IQR: 12-51). There were no significances in outcomes in cohort 2, while in cohort 1 PDGFR (adjusted HR: 30.41, 95% CI, 2.8->100) and p63 (adjusted HR: 0.12, 95% CI, 0.02-0.87) were associated with PFS while only p63 retained significance for OS in UVA (p=0.005, HR hardly estimable due to small numbers). BMKs were independent each other and of clinical variables. Conclusions A significant proportion of UC pts harbor potentially druggable targets, although it is unclear if targeting them translates to improved outcomes. New signals were obtained in relation to prognosis of UC, partly discordant with available literature. A greater sample size and a validation cohort will be required to confirm the prognostic significance of PDGFR and p63 in patients undergoing peri-operative treatment. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e499-e500 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Andrea Necchi More articles by this author Patrizia Giannatempo More articles by this author Biagio Paolini More articles by this author Luigi Mariani More articles by this author Elena Farè More articles by this author Daniele Raggi More articles by this author Nicola Nicolai More articles by this author Luigi Piva More articles by this author Mario Catanzaro More articles by this author Davide Biasoni More articles by this author Tullio Torelli More articles by this author Silvia Stagni More articles by this author Massimo Maffezzini More articles by this author Alessandro Gianni More articles by this author Maurizio Colecchia More articles by this author Roberto Salvioni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...