Fluorescence In Situ Hybridization Aneuploidy as a Predictor of Clinical Disease Recurrence and Prostate-Specific Antigen Level 3 Years After Radical Prostatectomy

Abstract

To determine if fluorescence in situ hybridization (FISH) analysis of fresh-tissue biopsy specimens obtained at the time of radical prostatectomy is able to predict prospectively clinical disease progression or prostate-specific antigen (PSA) level in patients 3 to 4 years after surgery. FISH analysis was performed on fresh-tissue touch preparations obtained from 90 randomly selected radical prostatectomy specimens. Cut surface touch preparations from 40 specimens resected in 1992 were analyzed with DNA probes for chromosomes 4, 6-12, 17, 18, X, and Y. Needle-biopsy specimens were obtained from 50 tumors resected in 1993, and touch preparations from these specimens were studied with DNA probes for chromosomes 7, 8, 11, and 12. Serum PSA levels and clinicopathologic data were recorded, and each patient was followed up from the time of surgery to determine cancer progression. Of 90 patients undergoing radical prostatectomy in 1992 and 1993, 89 returned for follow-up. Three patients received preoperative hormonal therapy, and in 2 patients, antiandrogen therapy was continued postoperatively. Fifteen patients underwent intraoperative orchiectomy immediately after radical prostatectomy, while 9 patients had postoperative adjuvant hormonal therapy. Six patients underwent postoperative radiation therapy. Fourteen patients (15.7%) demonstrated systemic, local, or PSA progression. Only 2 (4.7%) of 43 patients with FISH diploid tumors demonstrated cancer progression. Conversely, 10 (30.3%) of 33 FISH aneuploid and 12 (26.1%) of 46 FISH nondiploid tumors demonstrated cancer progression (P=.004 and P=.006, respectively). Unlike FISH, flow cytometric aneuploidy was not associated with early cancer progression. Elevated preoperative PSA concentration, increased preoperative and postoperative Gleason score, and increased preoperative and postoperative T or N stage were not statistically significantly associated with cancer progression. While chromosome 7 and 8 aneusomies were not statistically associated with cancer progression, 2 of 5 (P=.04) chromosome 12 aneusomic tumors demonstrated cancer progression. Early (within 4 years) local, systemic, or PSA progression occurred more frequently (P<.05) in radical prostatectomy patients with FISH aneuploid, nondiploid, and chromosome 12 aneusomic tumors. Flow cytometric ploidy status, preoperative serum PSA concentration, and clinical or pathologic grade or stage, including seminal vesicle involvement, margin status, and capsular perforation status, were not associated with early prostate cancer progression in this group of 89 patients. FISH analysis appears to be a useful preoperative tool for predicting aggressive vs indolent prostate cancer.