Gene Panel Model Predictive Of Male Outcome At High Systemic Progression And Death Risk From Prostate Cancer After Radical Retropubic Prostatectomy

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology;  Men's health
Article Date: 26 Sep 2008 - 4:00 PDT

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UroToday.com - In the August 20, 2008 issue of the Journal of Clinical Oncology, Dr. John C. Cheville and associates from the Mayo Clinic proposed a predictive model, that includes genetic markers, for men at high risk of prostate cancer progression after radical prostatectomy (RP).

From 1990-2004, patients treated with RP at the Mayo clinic were selected for inclusion. Initial analysis was performed on laser capture micro-dissected prostate cancer specimens for which candidates' genes were identified using microarray expression. Tumor ploidy and clinical and pathologic variables were included in the model. Evaluating a high risk cohort of patients with Gleason score 7-10 tumors, the strongest significant clinical predictors of time to systemic progression were Gleason score, seminal vesicle invasion and lymph node metastasis with a concordance statistic of 0.69. This was lower than the 0.82 value for the overall group and suggested that the model could be improved upon by including molecular marker panels.

A set of 38 genes was selected from the microarray experiments. Cases were matched to controls for the model, and hierarchical clustering was performed for the normalized genes. As a binary variable, the ETS fusion gene status of a patients' tumor was included. In the best model, the genes TOP2A, CDH10, ploidy, and predicted fusion status resulted in an area under the curve (AUC) of 0.81. Independent validation was performed using frozen tumors from a separate cohort of 57 high risk patients. The AUC for this group was 0.79. This model increases the predictive accuracy of identifying men at higher risk for disease progression and death following RP.

Cheville JC, Karnes RJ, Therneau TM, Kosari F, Munz JM, Tillmans L, Basal E, Rangel LJ, Bergstralh E, Kovtun IV, Savci-Heijink CD, Klee EW, Vasmatzis G

J Clin Oncol. 2008 Aug 20;26(24):3930-6
10.1200/JCO.2007.15.6752

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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