Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential

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• 作者：Eric A. Klein^a ; ^&dagger ; ; ^{kleine@ccf.org} ; Marí ; a Santiago-Jimé ; nez^b ; ^&dagger ; ; Kasra Yousefi^b ; ^&dagger ; ; Bruce A. Robbins^c ; Edward M. Schaeffer^e ; ^&dagger ; ; Bruce J. Trock^f ; Jeffrey Tosoian^f ; Zaid Haddad^b ; ^&dagger ; ; Seong Ra^c ; R. Jeffrey Karnes^g ; Robert B. Jenkins^h ; John C. Cheville^h ; Robert B. Denⁱ ; Adam P. Dickerⁱ ; Elai Davicioni^b ; ^&dagger ; ; Stephen J. Freedland^d ; ^j ; ^&dagger ; ; Ashley E. Ross^f ; ^&dagger ;
• 关键词：prostatic neoplasms ; neoplasm grading ; genomics ; watchful waiting ; neoplasm metastasis
• 刊名：The Journal of Urology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：197
• 期：1
• 页码：122-128
• 全文大小：1189 K
• 卷排序：197

文摘

We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential.Materials and MethodsWe analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05.ResultsOf men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09–0.42) compared to 0.30 (IQR 0.17–0.42) in patients with pT3 disease or positive margins (p = 0.005).ConclusionsUsing a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup.