EXTENSIVE GENETIC ALTERATIONS IN PROSTATE-CANCER REVEALED BY DUAL PCRAND FISH ANALYSIS

The genetic alterations that underlie prostate tumorigenesis are assum ed to comprise gain or loss of specific chromosomal regions, whole chr omosomes, or sequence-specific mutations. Existing data have not demon strated clear specificity of whole chromosome or regional chromosomal gain or loss that characterizes entire individual malignant lesions, o r all malignant lesions, within a cancerous prostate. We have analyzed tissues from 13 patients for target sequences by using PCR and FISH t echniques on paired malignant or prostatic intraepithelial neoplastic (PIN) and benign samples (usually from different areas of the same par affin section). We exercised stringent histologic control over these s amples by examining small (<5 mm2), discrete regions of sectioned beni gn, malignant, and PIN tissue. The same histologic region was examined on serial sections by FISH and PCR analysis. The tissues were examine d for numerical aberrations involving chromosomes 4 (as a control), 7, 8, 10, and the Y by FISH analysis, and for gain or loss of chromosome 7 and chromosomal arms 8p, 10q, and Yp by PCR analysis. The concurren t application of PCR and FISH to microdissected prostatic tissues yiel ded evidence of higher frequencies of genetic aberration in prostate c ancers than those found with either method alone or by other approache s. These results indicate the power of simultaneous genetic assays tha t are closely linked to specific tumor histology. (C) 1993 Wiley-Liss, Inc.