A Tri-Marker Proliferation Index Predicts Biochemical Recurrence after Surgery for Prostate CancerReport as inadecuate




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Prostate cancer exhibits tremendous variability in clinical behavior, ranging from indolent to lethal disease. Better prognostic markers are needed to stratify patients for appropriately aggressive therapy. By expression profiling, we can identify a proliferation signature variably expressed in prostate cancers. Here, we asked whether one or more tissue biomarkers might capture that information, and provide prognostic utility. We assayed three proliferation signature genes: MKI67 Ki-67; also a classic proliferation biomarker, TOP2A DNA topoisomerase II, alpha, and E2F1 E2F transcription factor 1. Immunohistochemical staining was evaluable on 139 radical prostatectomy cases in tissue microarray format, with a median clinical follow-up of eight years. Each of the three proliferation markers was by itself prognostic. Notably, combining the three markers together as a -proliferation index- 0 or 1, vs. 2 or 3 positive markers provided superior prognostic performance hazard ratio = 2.6 95% CI: 1.4–4.9; P = 0.001. In a multivariate analysis that included preoperative serum prostate specific antigen PSA levels, Gleason grade and pathologic tumor stage, the composite proliferation index remained a significant predictor P = 0.005. Analysis of receiver-operating characteristic ROC curves confirmed the improved prognostication afforded by incorporating the proliferation index compared to the clinicopathologic data alone. Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer.



Author: Sameer Malhotra , Jacques Lapointe , Keyan Salari , John P. Higgins, Michelle Ferrari, Kelli Montgomery, Matt van de Rijn, James

Source: http://plos.srce.hr/



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