CHROMOSOMAL-ANOMALIES IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND CARCINOMA DETECTED BY FLUORESCENCE IN-SITU HYBRIDIZATION

The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We used fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in PIN (68 foci), localized prostatic carcinoma (78 foci), and lymph node metastases (8 foci) in 40 whole-mount radical prostatectomy and pelvic lymphadenectomy specimens. Chromosomal anomalies were found in 50, 51, and 100% of the foci of PIN;, carcinoma, and metastases, respectively. The mean numbers of abnormal chromosomes per focus were 0.66 in PIN, 1.09 in carcinoma, and 3.75 in metastases. The most frequent anomaly in PIN was a gain of chromosome 8 (32% of foci), followed by gains of chromosomes 10 (13%), 7 (10%), 12 (4%), and Y (4%). The most frequent anomalies in foci of carcinoma were gains of chromosomes 7 and 8 (28% and 30% of foci, respectively), followed by gains of chromosomes 10 (23%), 12 (9%), and Y (9%). There was a positive correlation of the gain of chromosome 8 with the pathological stage and Gleason score (both P < 0.05). Usually, carcinoma foci contained more anomalies than paired PIN foci, but five prostates contained one or more foci of PIN with more anomalies than carcinoma. Among the cases with metastases, usually one or more foci of the primary tumor shared chromosomal anomalies with the matched metastases. Our results indicate that PIN and prostatic carcinoma foci have similar proportions of chromosomal anomalies, but foci of carcinoma usually have more alterations. This observation supports the hypothesis that PIN is often a precursor of carcinoma, although there are some carcinoma foci that have few or no apparent chromosomal alterations, whereas concurrent PIN foci have multiple alterations. A gain of chromosome 8 was the most common numerical alteration and was associated with increasing cancer stage and grade, suggesting that it may play a role in the initiation and progression of prostatic carcinoma. Usually, one or more foci of the primary tumor shared chromosomal anomalies with associated lymph node metastases, suggesting that, often, just a single focus of carcinoma gives rise to metastases.