Faculty Bibliography

OBJECTIVES/OBJECTIVE:To correlate the primary Gleason pattern among patients with biopsy-derived Gleason 7 tumors with the radical prostatectomy specimen Gleason grading and other clinical and pathologic outcomes. METHODS AND MATERIALS/METHODS:Among 474 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1997-2001, 205 (43%) had Gleason 7/10 tumors on pre-operative needle biopsy. Among theses patients, 148 (72.2%) were assigned a primary Gleason 3 pattern (3+4 = 7) and 57 (27.8%) were assigned a primary Gleason 4 pattern (4+3 = 7). The two groups were compared with respect to age, serum PSA levels, Gleason grade in the radical prostatectomy specimen, pathological stage and surgical margin status. RESULTS:Among patients with 3+4 tumors on needle biopsy, 64% remained primary Gleason grade 3 while 35% were up-graded to a primary pattern 4 following analysis of the radical prostatectomy specimen. Patients with 4+3 tumors on needle biopsy remained primary Gleason grade 4 in 51% of patients, while 49% of patients had their tumors down-graded to a primary 3 pattern (p = 0.09). There were no differences between patients with needle biopsy 3+4 and 4+3 patterns with respect to total Gleason score in the radical prostatectomy specimen (p = 0.42), pTNM stage (p = 0.36), extra-prostatic extension (p = 0.88), surgical margin involvement (p = 0.16), and seminal vesicle invasion (p = 0.19). In contrast, the primary Gleason pattern in the radical prostatectomy specimen correlated significantly with pTNM stage (p = 0.02) and seminal vesicle invasion (p= 0.003), but not with extra-prostatic extension (p = 0.32) and surgical margin involvement (p = 0.17). CONCLUSIONS:Among patients with Gleason 7 adenocarcinoma of the prostate, the biopsy-derived primary Gleason pattern does not appear to correlate with important clinical and pathologic outcomes. The utility of distinguishing a primary Gleason pattern on needle biopsy among patients with Gleason 7 tumors remains unclear given the limited and conflicting literature addressing this issue.

Metaphase-based comparative genomic hybridization (CGH) has identified recurrent regions of gain on different chromosomes in bladder cancer, including 6p22. These regions may contain activated oncogenes important in disease progression. Using quantitative multiplex polymerase chain reaction (QM-PCR) to study DNA from 59 bladder tumors, we precisely mapped the focal region of genomic gain on 6p22. The marker STS-X64229 had copy number increases in 38 of 59 (64%) tumors and the flanking markers, RH122450 and A009N14, had copy number gains in 33 of 59 (56%) and 26 of 59 (45%) respectively. Contiguous gain was present for all three markers in 14 of 59 (24%) and for two (RH122450 and STS-X64229) in 25 of 59 (42%). The genomic distance between the markers flanking STS-X64229 is 0.5 megabases, defining the minimal region of gain on 6p22. Locus-specific interphase fluorescence in situ hybridization confirmed the increased copy numbers detected by QM-PCR. Current human genomic mapping data indicates that an oncogene, DEK, is centrally placed within this minimal region. Our findings demonstrate the power of QM-PCR to narrow the regions identified by CGH to facilitate identifying specific candidate oncogenes. This also represents the first study identifying DNA copy number increases for DEK in bladder cancer.

Reports of primary large cell neuroendocrine carcinomas of the urinary bladder are few; we identified only 2 cases in the literature. Both of these cases involved male patients with rapid progression of disease culminating in death with widespread metastases. We report a case of primary large cell neuroendocrine carcinoma of the bladder, with an admixed minor element of adenocarcinoma, in an 82-year-old man. This solitary lesion arose in a bladder diverticulum lateral to the left ureteric orifice. Two attempts at transurethral resection were unsuccessful at achieving local control. The patient underwent a partial cystectomy with left-sided pelvic lymphadenectomy following preoperative staging investigations that found no metastatic disease. Pathologically, the tumor invaded into the deep aspect of the muscularis propria, without extension into perivesical fat. The lateral resection margin was microscopically positive for tumor, but no malignancy was found in the pelvic lymph nodes. The adenocarcinoma comprised less than 5% of total tumor volume, and areas of transition between the neuroendocrine and adenocarcinoma components were apparent. The patient developed a local recurrence 8 months postoperatively, which was managed by a combination of transurethral resection and radiation therapy. Currently, the patient has no evidence of local or metastatic disease 2 years after initial diagnosis.