Expression of DC-SCRIPT/ZNF366 Protein in Prostatic Adenocarcinomas (PACS): DC-SCRIPT Signaling Is Associated with High Tumor Grage, Advanced Stage and Biochemical Disease Recurrence
Wadad Mneimneh, Bhaskar VS Kallakury, Gregory M Sheehan, Michael Feurstein, Christine E Sheehan, Hugh AG Fisher, Ronald P Kaufman, Tipu Nazeer, Jeffrey S Ross. Albany Medical College, Albany, NY; Georgetown University Hospital, Washington, DC
Background: Dendritic cell specific transcript, a novel protein encoded by an 8-kb mRNA, is a transcription coregulator which upon binding to hormones, plays a key role in physiologic processes including growth and differentiation. DC-Script expression has been shown to have an independent prognostic value in the development and progression of human breast cancer. However, studies on DC-script protein expression in human carcinogenesis are extremely limited with almost no available data on its prognostic value in any other human cancers including prostatic carcinoma. In this study, we evaluated DC-script protein expression by immunohistochemistry in human prostatic adenocarcinoma and correlated staining results with standard prognostic variables such as tumor grade, stage and disease recurrence.
Design: Formalin-fixed, paraffin-embedded sections from 132 PACs were immunostained by automated methods (Ventana) using goat anti-human DC-SCRIPT/ZNF366 antibodies (R&D Systems, Minneapolis, MN). Cytoplasmic immunoreactivity was scored based on intensity and percentage of positive cells, in a semi-quantitative scoring system, in both tumor and adjacent benign epithelium of each case. Moreover, tumor and benign tissue scores were compared in each case, and cases were subsequently classified accordingly in three categories: tumor (T) = benign (B) T=B, T>B, and T < B. Results were correlated with clinicopathologic variables.
Results: Cytoplasmic DC-SCRIPT immunoreactivity was noted as follows: [T>B 87/132 (66%), T=B 45/132 (34%), T < B 0%] and correlated with high grade [76% high grade vs 59% low grade, p=0.043] and advanced stage [ 79% advanced vs 61% early, p=0.047]. Intense diffuse tumor immunoreactivity was noted in 26/132 (20%) [all 26 cases were in the T>B subgroup; 26/87 (30%) of all T>B cases] and correlated with high grade [28% high grade vs 14% low grade, p=0.052] and biochemical disease recurrence [29% recur vs 11% non-recur, p=0.011]. On multivariate analysis, intense diffuse tumor immunoreactivity (p=0.05) and advanced stage (p=0.009) independently predicted biochemical disease recurrence.
Conclusions: These findings indicate that, similar to studies in breast cancer, DC-script protein expression is an independent adverse prognostic factor for patients with surgically resected prostate cancer. Further study of this transcriptional regulator and correlation with hormonal therapy response appears warranted.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 151, Monday Morning