High-grade prostate intraepithelial neoplasia shares cytogenetic alterations with invasive prostate cancer

BACKGROUND. High-grade prostate intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma. However, the relationship bet ween this lesion and prostate cancer has not yet been established. The dete ction of cytogenetic changes in the lesions prior to prostate adenocarcinom a would be useful in demonstrating such a pathogenic relationship. METHODS. Twenty eight high-grade PIN cases were found among 57 specimens of radical prostatectomy performed for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH) analysis using centromeric probes to enumerate chromosomes 7, 8, 10, and 12 was performed to study the numer ical chromosome alterations. FISH analysis was carried out over isolated nu clei obtained from high-grade PIN areas and prostate cancer foci in the sam e prostatectomy specimen. RESULTS. Of the 28 suitable casts it was possible to complete the study in 26 tumor and 20 PIN areas. The remaining cases were excluded because of ins ufficient tissue or poor preservation. Cytogenetic alterations (aneuploidy) were found in 16 of the 26 (62%) tumors studied. The most frequent chromos ome alteration was trisomy 7, detected in 12 (7570) aneuploid tumors, follo wed by monosomy 8 present in 5 (31%) aneuploid tumors. Trisomy 7 was also t he most frequent isolated chromosome alteration since it was detected in 7 (44%) tumors. Thirteen of 20 (65%) PIN cases were aneuploid when studied by FISH. Trisomy 7, trisomy 8, and monosomy 8 were the most common cytogeneti c alterations in the 20 PIN areas studied, being observed in nine (45%), si x (30%), and four (20%) cases, respectively. FISH analysis showed a high co rrelation (75% cases) in ploidy and pattern of cytogenetic alterations betw een high-grade PIN areas and the paired prostate cancer focus in the same s pecimen. CONCLUSIONS. The above results show a cytogenetic link between high-grade P IN and prostate cancer, suggesting that the former could be an early form o f prostate cancer. Prostate 47:29-35,2001. (C) 2001 Wiley-Liss,Inc.