Molecular cytogenetic analysis of prostatic adenocarcinomas from screeningstudies - Early cancers may contain aggressive genetic features

No objective parameters have been found so far that can predict the biologi cal behavior of early stages of prostatic cancer, which are encountered fre quently nowadays due to surveillance and screening programs. We have applie d comparative genomic hybridization to routinely processed, paraffin-embedd ed radical prostatectomy specimens derived from patients who participated i n the European Randomized Study of Screening for Prostate Cancer. We define d a panel consisting of 36 early cancer specimens: 13 small (total tumor vo lume (T-v < 0.5 ml) carcinomas and 23 intermediate (T-v between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, lar ge T-v > 2.0 ml) tumor samples, not derived from the European Randomized St udy of Screening for Prostate Cancer. Chromosome arms that frequently (ie, greater than or equal to 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, greater than or equal t o 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was de tected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). N o consistent gains were found in this group. In the large tumors, loss was seen of 13q (69%), 8p (50%), 5q, 6q (both 31%), and Y (15%). Gains were obs erved of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of th ese early, localized tumors with large adenocarcinomas showed a significant increase in the number of aberrant chromosomes per case (R-s = 0.36,P = 0. 009). The same was true for the number of lost or gained chromosomes per ca se (R-s = 0.27, P = 0.05; R-s = 0.48, respectively; P < 0.001). Interesting ly, chromosomal alterations that were found in previous studies to be poten tial biomarkers for tumor aggressiveness, le, gain of 7pq and/or 8q, were a lready distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically off 6q and 13q, ar e early events in prostatic tumorigenesis, whereas chromosomal gains, espec ially of 8q, appear to be late events in prostatic tumor development. Final ly, early localized tumors, as detected by screening programs, harbor cance rs with aggressive genetic characteristics.