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(American Journal of Pathology. 2001;158:399-406.)
© 2001 American Society for Investigative Pathology

Short Communication

Molecular Cytogenetic Analysis of Prostatic Adenocarcinomas from Screening Studies

Early Cancers May Contain Aggressive Genetic Features

Janneke C. Alers^*, Pieter-Jaap Krijtenburg^*, André N. Vis^*, Robert F. Hoedemaeker^*, Mark F. Wildhagen, Wim C. J. Hop, Theodorus H. van der Kwast^*, Fritz H. Schröder, Hans J. Tanke^§ and Herman van Dekken^*

From the Departments of Pathology,^*
Urology,
and Epidemiology and Biostatistics,
Erasmus University Medical Center Rotterdam, Rotterdam; and the Laboratory for Cytochemistry and Cytometry,^§
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (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, large (T_v > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No 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 observed of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of these 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 case (R_s = 0.27, P = 0.05; R_s = 0.48, respectively; P < 0.001). Interestingly, chromosomal alterations that were found in previous studies to be potential biomarkers for tumor aggressiveness, ie, gain of 7pq and/or 8q, were already distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically of 6q and 13q, are early events in prostatic tumorigenesis, whereas chromosomal gains, especially of 8q, appear to be late events in prostatic tumor development. Finally, early localized tumors, as detected by screening programs, harbor cancers with aggressive genetic characteristics.

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