Potential markers of aggressiveness in prostatic intraepithelial neoplasia detected by fluorescence in situ hybridization

Objective: High-grade prostatic intraepithelial neoplasia (PIN) represents the most likely precursor of prostatic adenocarcinoma. In this review, we discuss the utility of different techniques of interphase fluorescence in situ hybridization (FISH) in evaluating the genetic association between PIN and adenocarcinoma. Methods and Results: Although the proportion of PIN and prostatic carcinoma foci that have chromosomal anomalies is similar, foci of carcinoma often have more alterations. This supports the hypothesis that PIN is a precursor of carcinoma. In some prostates, however, PIN foci have more alterations than matched carcinoma foci, suggesting that PIN foci can sometimes undergo more extensive chromosome evolution than carcinoma foci. Gain of chromosome 8 is the most common numerical alteration in prostatic carcinoma and PIN foci, and is associated with increasing cancer stage and grade. Thus, genes on chromosome 8 may play a role in the initiation and progression of prostatic carcinoma. One primary tumor focus usually shares chromosomal anomalies with associated lymph node metastases, implying that only one primary lesion acquires genetic alterations that allow it to escape the prostate. Conclusions: PIN and prostatic carcinoma have similar genetic changes. This supports the hypothesis that PIN is often a precursor of carcinoma. Genes on chromosome 8 may play a role in both initiation and progression of prostatic carcinoma.