Pan-cadherin as a high level phenotypic biomarker for prostate cancer.

Abstract

High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.