Recent evidence shows that the proportion of poorly differentiated prostate
carcinoma (Gleason pattern [
GP] 4/5) is a surrogate factor for biochemical failure after radical
prostatectomy (RP). However, little is known about specific molecular and cytogenetic changes in this aggressive component of localized
prostate cancer. We constructed a tissue microarray containing areas of GP 3 and 4 from
formalin-fixed radical
prostatectomy specimens of 39 patients with Gleason score 7
carcinoma (>or=50%
GP 4), known pathologic staging parameters (stage < T3b), and biochemical failure data (mean follow-up, 30 months; range, 5 to 74 months). Interphase fluorescent in situ hybridization (FISH) was performed on 5-microm microarray sections using pericentromeric probes to chromosomes 7, 8, and 17 and probes for the HER-2/neu and
epidermal growth factor receptor (EGFR) genes. Low-level amplification of HER-2/neu was found in 26% of cases (3 to 5 signals per nucleus, corrected for chromosome 17 aneusomy). Aneusomy of chromosomes 7, 8, and 17 was identified in 21%, 15%, and 5% of cases, respectively. All aberrations occurred almost exclusively in
GP 4 carcinoma (8 of 8 aneusomies 7, 2 of 2
trisomies 17, 9 of 10 HER-2/neu amplifications, and 5 of 6 aneusomies 8; P < .001). The presence of HER-2/neu amplification was associated with high
tumor volume (>2.0 cm(3), P = 0.004). Among patients with
negative surgical margins, gain of chromosome 7 was associated with biochemical failure after RP (P =.004, log-rank). Amplification of the EGFR gene occurred in only 1 case (3%). Significant differences in HER-2/neu amplification and gain of chromosomes 7, 8, and 17 were detected between
GP 4 prostate
carcinoma and GP 3. The frequency of aberrations increased with
tumor volume. Chromosome 7 abnormalities may play an important role in
cancer progression in margin-negative patients. EGFR amplification was rare, suggesting that this oncogene is not altered at the gene copy number level.