Abstract 4343: Prognostic significance of CBP (CREB-binding protein) in prostatic adenocarcinomas (PACs): CBP is associated with high grade, advanced stage and biochemical disease recurrence
Authors: Ross Jeffrey S. , Voronel Olga , Dalvi Siddhartha , Sheehan Gregory M. , Sheehan Christine E. , Nazeer Tipu , Kallakury Bhaskar VS 
Published: August 2015

Background: CREB-binding protein (CBP), encoded by the CREBBP gene functions as an activator of a variety of transcription factors that play critical roles in normal embryonic growth and development, tumorigenesis and homeostasis by coupling chromatin remodeling to transcription factor recognition. Whether CBP functions as a tumor suppressor or an oncogene in cancer progression remains unclear. In this study, we assessed the prognostic significance of CBP protein expression in PACs.

Design: Formalin-fixed paraffin-embedded tissue sections from 115 PACs were immunostained by a manual method (DAKO EnVision+ Dual Link System-HRP) using rabbit polyclonal CBP (Santa Cruz Biotech, Santa Cruz, CA). Cytoplasmic and/or nuclear immunoreactivity was scored based on intensity and percentage of positive cells in both the tumor (T) and adjacent benign (B) epithelium in each case. Cases were assessed as tumor&gt;benign (T&gt;B), tumor = benign (T = B), tumor&lt;benign (T&lt;B) or negative (N). Results were correlated with clinicopathologic variables.

Results: Cytoplasmic CBP immunoreactivity was observed as follows: T&gt;B 41%, T = B 37%, T&lt;B 2% N 20%; and correlated with high (HG&gt; = Gleason 7) vs low (LG&lt; = Gleason 6) tumor grade [T&gt;B 52% HG vs 33% LG, T = B 19% HG vs 51% LG, T&lt;B 2% HG vs 1% LG, N 27% HG vs 15% LG; p = 0.006] and advanced (stage III,IV) vs early (stage I, II) tumor stage [T&gt;B 51% adv vs 31% early, T = B 23% adv vs 52% early, T&lt;B 2% adv vs 2% early, N 24% adv vs 15% early; p = 0.016]; and biochemical disease recurrence [T&gt;B 53% recurr vs 28% non recurr, T = B 26% recurr vs 49% non recurr, T&lt;B 2% recurr vs 2% non recurr, N 19% recurr vs 21% non recurr; p = 0.033]. Nuclear CBP immunoreactivity was observed as follows: T&gt;B 42%, T = B 7%, T&lt;B 0% N 51%; and correlated with high (HG&gt; = Gleason 7) vs low (LG&lt; = Gleason 6) tumor grade [T&gt;B 58% HG vs 30% LG, T = B 6% HG vs 7% LG, N 36% HG vs 63% LG; p = 0.008] and advanced (stage III, IV) vs early (stage I, II) tumor stage [T&gt;B 54% adv vs 29% early, T = B 7% adv vs 7% early, N 39% adv vs 64% early; p = 0.019]. On multivariate analysis, high tumor grade independently predicted biochemical disease recurrence (p = 0.006).

Conclusion: CBP immunoreactivity is a biomarker of adverse prognosis in PAC, correlating with high tumor grade and advanced stage disease. Cytoplasmic CBP expression is also associated with biochemical disease recurrence. Further study of CBP expression and its potential role in prostate cancer appears warranted.

Citation Format: Jeffrey S. Ross, Olga Voronel, Siddhartha Dalvi, Gregory M. Sheehan, Christine E. Sheehan, Tipu Nazeer, Bhaskar VS Kallakury. Prognostic significance of CBP (CREB-binding protein) in prostatic adenocarcinomas (PACs): CBP is associated with high grade, advanced stage and biochemical disease recurrence. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4343. doi:10.1158/1538-7445.AM2015-4343