DNA-PLOIDY IN PROSTATE-CANCER - POTENTIAL MEASUREMENT AS A SURROGATE END-POINT BIOMARKER

Measurements of DNA ploidy have considerable promise for serving as su rrogate endpoint biomarkers (SEBs) for prostate carcinoma. Studies of benign prostatic hypertrophy (BPH) tissue by flow cytometry (FCM), ima ge analysis, and fluorescent in situ hybridization (FISH) for ploidy i nvariably show normal DNA content and chromosome numbers. In contrast, most aggressive prostate cancers are aneuploid, particularly when new , sensitive methodologies are applied. Certain tumors which have appea red to be DNA diploid by FCM can be shown to be aneuploid with only on e or a few abnormal chromosomes by FISH studies. Certain cases of pros tatic intraepithelial neoplasia (PIN) are also known to be aneuploid b y FISH ploidy using alpha satellite probes for centromere counting. Th e latest data suggest abnormalities of chromosomes 7 and 8 are most fr equently detected.Therefore, a surrogate endpoint assay which detects aneusomies of chromosomes 7 or 8 in histologically normal or dysplasti c prostate tissue might serve as a very significant intermediate endpo int biomarker to identify neoplastic prostate cells on their way to be coming clinically aggressive prostate carcinomas. (C) 1994 Wiley-Liss, Inc.