[959] Activating Transcription Factor 3 (ATF3) Protein Expression in Prostatic Adenocarcinomas (PAC)

JS Ross, C Yan, GM Sheehan, CE Sheehan, T Nazeer, HAG Fisher, BM Mian, BVS Kallakury. Albany Medical College, Albany, NY; Georgetown University Hospital, Washington, DC

Background: Human transcription factor ATF3 is involved in gene expression by its binding to the cAMP response element. ATF3 has been shown to be upregulated as an intracellular response to various stresses including DNA damage. ATF3 expression has been associated with mouse esophageal and mammary tumorigenesis, but there are no reports of comprehensive analysis in human cancers. In this study, we evaluate, for the first time, the prognostic significance of ATF3 expression in human PAC.
Design: Formalin-fixed paraffin-embedded tissue sections from 149 PAC were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using polyclonal rabbit anti-human ATF3 antibody (clone C-19; Santa Cruz, Santa Cruz, CA). Cytoplasmic and nuclear immunoreactivity was semi-quantitatively scored based on intensity and percentage of positive cells in both the tumor and adjacent benign epithelium in each case. Scoring was based on staining intensity and percentage of positive cells. A multiplicative index was calculated and cases were assessed as tumor=benign baseline (T=B), tumor>benign (T>B) and tumorResults: Variable cytoplasmic and nuclear ATF3 immunoreactivity was noted in the tumor and adjacent benign basal cells and secretory epithelium in all cases. Cytoplasmic ATF3 protein was expressed as follows [T=B 58%, T>B 39%, TB 52% HG vs 30% LG, TB 59% HG vs 25% LG, TB 53% recur vs 31% non-recur, TB 25%, TB 40% HG vs 15% LG, TB cytoplasmic ATF3 protein expression (p=0.016) independently predicted biochemical disease recurrence.
Conclusions: ATF3 over-expression is associated with high grade, advanced stage PAC and independently predicts biochemical disease recurrence. Further study of ATF3 expression as both a prognostic factor and potential target of therapy for PAC appears warranted.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 96, Wednesday Morning