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Genitourinary Advanced Pca and Its Efficacy As a Therapeutic Agent Is Presently Being Studied in Clinical Trials

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ANNUAL MEETING ABSTRACTS 133A because they were over age 80 and as such, the IHC results were likely due to acquired 599 Anterior Predominant Prostate Tumors: A Contemporary methylation of the MLH1 promoter. The remaining 4 patients with absent staining have Look at Zone of Origin been referred to Cancer Genetics for possible further work-up. The reimbursement rate HA Al-Ahmadie, SK Tickoo, A Gopalan, S Olgac, VE Reuter, SW Fine. Memorial Sloan and turn-around time for the IHC stains were similar to that for other IHC stains used Kettering Cancer Center, NY, NY. in clinical practice. Background: Aggressive PSA screening and prostate needle biopsy protocols have Conclusions: IHC stains for the MMR proteins are fast and relatively easy to institute in successfully detected low-volume posterior tumors, with a concurrent increase in routine evaluation of CRC, and we have not had difficulty interpreting the stains leading anterior-predominant prostate cancer (AT). Zone of origin, patterns of spread, and to additional testing. Furthermore, reimbursement was obtained at a level similar to extraprostatic extension of these tumors have not been well studied. other IHC stains used in clinical practice. The surgeons and oncologists welcomed the Design: We greatly expanded and refined our previous studies to include pathologic prognostic information. Further study is warranted to confirm these initial findings. features of 197 patients with largest tumors anterior to the urethra in whole-mounted radical prostatectomy specimens. 597 High Fidelity Image Cytometry in Neoplastic Lesions in Barrett’s Results: Of 197 AT, 97 (49.2%) were predominantly located in the peripheral zone Esophagus, Including Basal Crypt Dysplasia-Like Atypia with Surface (PZ-D), 70 (35.5%) in the transition zone (TZ-D), 16 (8.1%) were of indeterminate Maturation zone (IND), and 14 (7.1%) in both PZ and TZ (PZ+TZ). PZ-D tumors: 34/97 (35%) = X Zhang, Q Huang, R Goyal, RD Odze. VA Boston Health Care System, Boston, MA; Gleason score (GS) 6, 61 (62.9%) = GS 7, and 2 = GS 9; 49 (50.5%) involved anterior Brigham and Women’s Hospital, Boston, MA. fibromuscular stroma (AFMS); 83 (85.6%) were organ confined (OC) and 11 (11.3%) Background: Chromosomal instability and DNA aneuploidy is a key event in the had extraprostatic extension (EPE), with invasion of anterior/anterolateral fat; 4 EPE progression of cancer in Barrett’s esophagus (BE). Automated image cytometry using cases also had a positive anterior margin (M+); 63 (64.9%) invaded the apical-most high fidelity DNA histograms have been shown to be more sensitive and less susceptible section, 11 with apical M+; 88 (90.7%) showed additional tumors of posterior PZ origin to technical and interpretation issues than flow cytometry for analyzing cellular DNA (GS 6: 66, GS 7: 21, GS 8: 1; posterior EPE: 3; posterior M+: 2). TZ-D tumors: 24/70 content. Basal crypt dysplasia-like atypia (BCDA), with surface maturation, has recently (34.3%) = GS 6 and 46 (65.7%) = GS 7; 52 (74.3%) involved AFMS; 60 (85.7%) were been reported to represent an early form of true dysplasia in BE. The aim of this study OC and 7 (10%) showed EPE, with invasion of anterior fat (7/7) and bladder neck [BN] was to evaluate DNA content in the progression of neoplasia in BE including cases of (2/7); 3 EPE cases and 3 OC tumors showed anterior M+; 46 (65.9%) invaded the BCDA, with surface maturation. apical-most section, 4 with apical M+; 64 cases (91.4%) showed additional PZ tumors Design: Eighty-two formalin fixed mucosal biopsies from 65 BE patients (M/F ratio: 6.3, (GS 6: 45, GS 7: 19; posterior EPE: 3; posterior M+: 2 [1 OC, 1 EPE]). IND tumors: mean age: 65 yrs.), representing the full range of neoplasia [negative (n = 2), indefinite 5/16 (31.2%) = GS 6 and 11 (68.8%) = GS 7; 13 involved the AFMS without clear (n = 2), BCDA (n = 14), low grade dysplasia (LGD, n = 17), high grade dysplasia (HGD, relationship to either TZ or PZ; 12 were OC, 4 had EPE with involvement of anterior n = 19), and adenocarcinoma (AD, n = 28)] were stained with H and E and Feulgen fat (4/4) and BN (1/4); 15 cases had additional PZ tumors (GS 6: 12; GS 7: 3). PZ+TZ: and evaluated for DNA content using an automated cellular imaging system (ACIS) 2/14 = GS 6 and 12 = GS 7; 12 were OC, 1 with anterior M+; 2 showed EPE, one with to generate high fidelity DNA histograms. Histograms consisted of DNA index (DI), anterior/apical M+; 10 involved AFMS; 8 involved the apical-most section, 1 with M+; representing integrated optical density relative to stromal cells in the same section and 13 had other PZ tumors (GS 6: 10; GS 7:3). were classified into diploid (peak DI = 0.9 – 1.1), mild aneuploidy (peak DI = 1.1 – 1.3), Conclusions: PZ-D tumors are more prevalent than TZ-D tumors in the anterior moderate aneuploidy (peak DI = 1.3 – 1.8), and severe aneuploidy (peak DI >1.8). prostate. AT of both zones show similar GS, EPE, and invasion of the apical portion Results: The prevalence of aneuploidy increased significantly (p<0.01) from negative/ of the prostate. TZ-D tumors more commonly involve AFMS. Tumor extension into indefinite (25%) to BCDA (57%), LGD (59%), HGD (100%) and AD (100%). Most anterior fat may represent definitive EPE in this region, where no clear capsule is present. aneuploid BCDA (87%) and LGD (100%) were mild in contrast to HGD (32%) and Prostates with AT frequently contain additional PZ tumors which are occasionally AD (0%), the majority of which showed either moderate (HGD: 26%, AD: 43%) or stage-determining. severe aneuploidy (HGD:42%, AD: 57%, p<0.01 vs BCDA or LGD). In addition, both cellular DNA content heterogeneity, and the distribution of cells with DNA content >5N, 600 Prostate Specific Membrane Antigen (PSMA) Expression in increased progressively from BCDA and LGD to HGD and AD (p<0.01). Primary Prostatic Adenocarcinoma: Comparison of Expression with Conclusions: High fidelity image cytometry provides objective discriminatory Gleason Grade and Hormonal Therapy information in BE-associated neoplastic lesions, and may be a useful adjunct to histology HA Al-Ahmadie, S Prakash, A Gopalan, S Olgac, SK Tickoo, SW Fine, HI Scher, VE and a potential marker of progression of neoplasia in this condition. Ploidy status of Reuter. Memorial Sloan-Kettering Cancer Center, New York, NY. BCDA is similar to that of LGD, which supports the concept that this abnormality Background: Prostate specific membrane antigen (PSMA) is a type II transmembrane represents an early neoplastic lesion in BE. glycoprotein that is consistently expressed in benign and neoplastic prostatic tissue with its strongest and most diffuse expression being in prostatic adenocarcinoma (PCa). Antibodies directed against PSMA are being utilized in imaging studies for patients with Genitourinary advanced PCa and its efficacy as a therapeutic agent is presently being studied in clinical trials. Previous studies have used proprietary antibodies with limited availability. Taking 598 Primary Carcinomas of the Urethra: A Clinicopathologic Analysis advantage of a recently developed and commercially available antibody, we studied of 100 Patients PSMA expression by immunohistochemistry (IHC) in a large number of hormone naïve primary PCa (PCaN) and after neoadjuvant therapy (PCaT). AJ Adeniran, P Tamboli, PE Spiess, HB Grossman, CPN Dinney, BA Czerniak. M.D. Design: Slides from tissue microarrays blocks prepared from formalin-fixed, paraffin- Anderson Cancer Center, Houston, TX. embedded archival material from prostatectomies performed at Memorial Sloan- Background: Primary urethral carcinomas are rare, accounting for <1% of urinary Kettering Cancer Center were stained by IHC with monoclonal antibody directed tract malignancies. Since most of these have been reported as small series or cases against the external domain of PSMA Clone 3E6 (Dako, Carpinteria, CA). The study reports, their clinical and morphologic spectrum remain incompletely defined, and their included 141 PCaN and 106 PCaT. Hormone-naïve non-neoplastic prostatic tissue behavoir is poorly understood. (NPN) from 316 cases and 66 cases of non-neoplastic prostatic tissue following Design: Retrospective review of all available material from 100 patients diagnosed with neoadjuvant therapy (NT) were also included. The extent and intensity of stain were primary urethral carcinoma at one center. Primary urethral carcinomas were defined as evaluated semi-quantitatively. tumors arising in the urethra; bladder tumors extending to the urethra were excluded. Results: Overall, PSMA expression was detected in 140 of 141 PCaN (99.3%). Results: Patient data: 29-85 year age range; 61 years median age; 3:2 male:female Expression increased in extent and intensity from NPN to PCaN and was most intense ratio. Median tumor size of 4 cm; 0.5-6.5cm range. Most common tumor location: and diffuse in tumors with high Gleason score (p ≤ 0.05) (Table.1). In PCaT, PSMA proximal urethra in females, bulbar urethra in males. Histological types included 27 expression was detected in 92 of 106 cases (86.8%). In non-neoplastic prostatic urothelial carcinoma (UC), 36 squamous cell carcinoma (SC), 17 adenocarcinoma (AC), acinar cells, PSMA expression was present in 86.7% and 92.4% of NPN and NT, 6 mixed carcinomas (MC), 11 carcinoma NOS (CN), 2 sarcomatoid carcinoma and 1 respectively. lymphoepithelioma-like carcinoma. AC included: 6 clear cell, 3 mucinous, 3 enteric, 2 Conclusions: Utilizing this commercially available antibody, the majority of PCa signet ring and 3 adenocarcinoma NOS. 7 tumors arose from urethral diverticula, 5 were express PSMA. This expression is stronger and more widespread in PCa with higher AC; 6 were in women.
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