DNA ploidy in prostate cancer: potential measurement as a surrogate endpoint biomarker

Measurements of DNA ploidy have considerable promise for serving as surrogate endpoint biomarkers (SEBs) for prostate carcinoma. Studies of benign prostatic hypertrophy (BPH) tissue by flow cytometry (FCM), image analysis, and fluorescent in situ hybridization (FISH) for ploidy invariably 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 appeared to be DNA diploid by FCM can be shown to be aneuploid with only one or a few abnormal chromosomes by FISH studies. Certain cases of prostatic intraepithelial neoplasia (PIN) are also known to be aneuploid by FISH ploidy using alpha satellite probes for centromere counting. The latest data suggest abnormalities of chromosomes 7 and 8 are most frequently detected. Therefore, a surrogate endpoint assay which detects aneusomies of chromosomes 7 or 8 in histologically normal or dysplastic prostate tissue might serve as a very significant intermediate endpoint biomarker to identify neoplastic prostate cells on their way to becoming clinically aggressive prostate carcinomas.