437 GAIN OF CHROMOSOME 8Q IS ASSOCIATED WITH METASTASES AND POOR SURVIVAL OF PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA (2012)

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2012437 GAIN OF CHROMOSOME 8Q IS ASSOCIATED WITH METASTASES AND POOR SURVIVAL OF PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA Tobias Klatte, Nils Kroeger, Edward Rampersaud, Frederic Birkhaeuser, Joshua Logan, Geoffrey Sonn, Joseph Riss, P. Nagesh Rao, Fairooz Kabbinavar, Arie Belldegrun, and Allan Pantuck Tobias KlatteTobias Klatte Los Angeles, CA More articles by this author , Nils KroegerNils Kroeger Los Angeles, CA More articles by this author , Edward RampersaudEdward Rampersaud Los Angeles, CA More articles by this author , Frederic BirkhaeuserFrederic Birkhaeuser Los Angeles, CA More articles by this author , Joshua LoganJoshua Logan Los Angeles, CA More articles by this author , Geoffrey SonnGeoffrey Sonn Los Angeles, CA More articles by this author , Joseph RissJoseph Riss Los Angeles, CA More articles by this author , P. Nagesh RaoP. Nagesh Rao Los Angeles, CA More articles by this author , Fairooz KabbinavarFairooz Kabbinavar Los Angeles, CA More articles by this author , Arie BelldegrunArie Belldegrun Los Angeles, CA More articles by this author , and Allan PantuckAllan Pantuck Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.504AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chromosome 8q harbors the proto-oncogene c-myc, which may be upregulated through gain of 8q and subsequently alter tumor biology through the MAPK/ERK pathway. In several malignancies, gain of 8q has been identified as an adverse prognostic factor, but there is no data in clear cell renal cell carcinoma (CCRCC). The objective of this study was to evaluate the prevalence of 8q gain in CCRCC and to correlate the findings with pathological variables and disease-specific survival (DSS). METHODS We prospectively analyzed the karyotypes of 393 consecutive patients who underwent nephrectomy for CCRCC at UCLA. Viable tumor samples were collected immediately after surgery, short-term cultured, and then cytogenetically analyzed by using GPG banding. The 336 patients (85%) with abnormal karyotype represent the reported study cohort. Comparisons of categorical data were performed with chi-square tests. Univariable and multivariable Cox proportional hazards models addressed the impact of 8q gain on DSS. RESULTS Gain of 8q occurred in 28 tumors (8%). Twelve tumors (43%) had unbalanced translocations, which involved the chromosomes 3p (n=3), 3q (n=2), 16q (n=2), 1p (n=1), 2q (n=1), 14q (n=1), 15p (n=1), and 19q (n=1). In addition, 9 tumors (32%) showed trisomy 8, and 7 (25%) had i(8)(q10), which resulted in loss of 8p (pter-p10) and gain of 8q (q10-qter). Both gain of 8q and loss of 8p were found in 11 tumors (39%). Gain of 8q was associated with a higher risk of regional lymph node metastases (21% vs. 6%, p=0.003) and distant metastases (50% vs. 24%, p=0.003), while no association was found with T stage (p=0.076) or grade (p=0.785). Patients with gain of 8q had worse prognosis (p=0.0001), corresponding to a 3.22-fold (95% CI 1.76-5.89) increased risk of RCC-specific death. In multivariable analysis, TNM stage group (HR 3.88, p<0.001), Fuhrman grade (HR 1.80, p=0.006) and gain of 8q (HR 1.95, p=0.034) were identified as independent prognostic factors. CONCLUSIONS Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. As the proto-oncogene c-myc is located on 8q, the current data suggest that tumors with gain of 8q and subsequent c-myc up-regulation may have unique molecular pathways activated, which are associated with an aggressive clinical phenotype. Defining tumors with gain of 8q may assist in identifying patients for specific c-myc inhibitors or agents targeting the MAPK/ERK pathway. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e179 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tobias Klatte Los Angeles, CA More articles by this author Nils Kroeger Los Angeles, CA More articles by this author Edward Rampersaud Los Angeles, CA More articles by this author Frederic Birkhaeuser Los Angeles, CA More articles by this author Joshua Logan Los Angeles, CA More articles by this author Geoffrey Sonn Los Angeles, CA More articles by this author Joseph Riss Los Angeles, CA More articles by this author P. Nagesh Rao Los Angeles, CA More articles by this author Fairooz Kabbinavar Los Angeles, CA More articles by this author Arie Belldegrun Los Angeles, CA More articles by this author Allan Pantuck Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...