Early prediction of disease progression in men with very low risk (VLR) prostate cancer who selected active surveillance (AS) rather than immediate treatment could reduce morbidity associated with overtreatment.
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We evaluated the association of six biomarkers [Periostin, (-5,-7) proPSA, CACNA1D, HER2/neu, EZH2, and Ki67] with different Gleason scores and biochemical recurrence (BCR) on prostate cancer tissue microarrays (TMAs) of 80 radical prostatectomy (RP) cases. Multiplex Tissue Immunoblotting (MTI) was used to assess these biomarkers in cancer and adjacent benign areas of 5µm sections. Multivariate logistic regression (MLR) was applied to model our results.
In the RP cases, CACNA1D, HER2/neu and Periostin expression were significantly correlated with aggressive phenotype in cancer areas. MLR model in cancer area yielded a ROC-AUC = 0. 98, while in cancer adjacent benign areas, yielding a ROC-AUC = 0. 94. CACNA1D and HER2/neu expression combined with Gleason score in a MLR model yielded a ROC-AUC = 0. 79 for BCR prediction. In the small biopsies from an AS cohort of 61 VLR cases, a MLR model for prediction of progressors at diagnosis retained (-5,-7) proPSA and CACNA1D, yielding a ROC-AUC of 0. 78, which was improved to 0. 82 after adding tPSA into the model.
Molecular profile of biomarkers is capable of accurately predicting aggressive prostate cancer on retrospective RP cases and identifying potential aggressive prostate cancer requiring immediate treatment on the AS diagnostic biopsy but limited in BCR prediction.
Comprehensive profiling of biomarkers using MTI predicts prostate cancer aggressive phenotype in RP and AS biopsies.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 Sep 24 [Epub ahead of print]
Guangjing Zhu, Zhi Liu, Jonathan I Epstein, Christine Davis, Christhunesa S Christudass, H Ballentine Carter, Patricia Landis, Hui Zhang, Joon-Yong Chung, Stephen M Hewitt, M Craig Miller, Robert W Veltri
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The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine. , Departments of Urology, Oncology, Pharmacology and Molecular Sciences, Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine. , Pathology, Johns Hopkins Medicine. , The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine. , Christian Medical College. , Departments of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine. , The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine. , Pathology, Johns Hopkins University. , Laboratory of Pathology, NCI. , Laboratory of Pathology, NCI. , Statistical Consultant. , The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine