Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization

Grading of the cribriform pattern of prostate cancer is controversial, and the genetic changes are largely unknown. Furthermore, the pathogenetic relationship between the cribriform pattern of high-grade prostatic intraepithelial neoplasia (PIN) and cribriform carcinoma is poorly understood. We used fluorescence in situ hybridization with centromere- specific probes for chromosomes 7, 8, 10, 12, and Y and a region-specific probe for c-myc to evaluate genetic changes in matched loci of high-grade PIN (48 foci) and prostatic carcinoma (71 loci) in 25 whole-mount radical prostatectomy specimens from patients with metastatic cancer. These cases included 10 foci of cribriform PIN and 10 loci of cribriform cancer. Numeric chromosomal anomalies were found in 67 and 68% of the high-grade PIN and carcinoma foci, respectively. Extra copies of the c-myc gene were identified in 52 and 44% of the high-grade PIN and carcinoma foci, respectively. The cribriform pattern of cancer had a higher percentage of loci with gain of chromosomes 7, 12, and Y, loss of chromosome 8, and extra copies of c-myc gene than other Gleason Primary Patterns 3 and 4; there was no difference, however, for all paired comparisons of genetic changes between the cribriform pattern of cancer and Gleason Primary Pattern 5 cancer. Cribriform PIN and cribriform cancer generally exhibited similar anomalies, although the percentage of foci with gain of chromosomes 10 and 12 was higher in cribriform cancer. Our results indicate that the cribriform pattern of prostate cancer shares genetic changes with Gleason Primary Pattern 5 and that both contain more genetic changes than the cribriform pattern of PIN. These findings suggest that the cribriform pattern of prostate cancer has biologic similarity with Gleason Pattern 5 carcinoma and that the cribriform pattern of PIN is closely associated with the cribriform pattern of prostatic carcinoma.