Genetic and chromosomal alterations in prostatic intraepithelial neoplasiaand carcinoma detected by fluorescence in situ hybridization

Objective: In this review, we discuss the utility of fluorescence in situ h ybridization (FISH) in the determination of genetic and chromosomal alterat ions in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as det ected by FISH and other techniques. Methods and Results: FISH is a commonly used technique for the determination of gene and chromosome dosage. In tis sue sections, FISH allows precise histopathologic correlation of multiple f oci of normal epithelium, premalignant lesions, and carcinoma within a sing le specimen, including study of intratumoral heterogeneity. PIN and prostat ic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common g enetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, part icularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncoge nes in these regions may be important for the initiation and progression of prostate cancer. Conclusions: FISH is a useful technique to determine gene tic relationships between cancer and its precursors. PIN and prostatic carc inoma foci have a similar proportion of genetic alterations, suggesting tha t PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progress ion of prostatic carcinoma.