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p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

Chandrakumar Shanmugam, Venkat R. Katkoori, Nirag C. Jhala, William E. Grizzle, Gene P. Siegal and Upender Manne

Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama (CS,VRK,NCJ,WEG,GPS,UM), and The UAB Comprehensive Cancer Center, Birmingham, Alabama (WEG,GPS,UM)

Correspondence to: Dr. Upender Manne, Associate Professor, Department of Pathology, The University of Alabama at Birmingham, 515B1-Kracke Building 619, 19th Street South, Birmingham, AL, 35294-7331. E-mail: manne{at}path.uab.edu

For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53^nac) and Bcl-2 expression are prognostic indicators. To understand their role in the progression of CRC we evaluated 90 CRCs and their contiguous adenomatous components (CAdCs) for immunohistochemical expression of these markers. In general, p53^nac and Bcl-2 expression was significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs that demonstrated p53^nac continued to express p53^nac in their contiguous CRCs. A similar trend was observed in Bcl-2 expression in that the majority of CAdCs expressing Bcl-2 continued to express it in their matching CRCs (39/44). Patients whose CAdCs and their contiguous CRCs demonstrate p53^nac had shorter median survival (35.9 months) than those patients whose CAdCs and CRCs did not (80.56 months). However, patients whose CAdCs had p53^nac and lacked Bcl-2 expression had the lowest median survival (15.74 months) when compared with patients whose CAdCs did not demonstrate p53^nac but had increased expression of Bcl-2 (71.77 months). These findings suggest that in those adenomas that demonstrate p53^nac but lack Bcl-2 expression, their contiguous CRCs are more likely to be aggressive as they progress. (J Histochem Cytochem 56:305–312, 2008)

Key Words: colorectal neoplasia • adenomatous component • p53 nuclear accumulation • Bcl-2 expression

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