p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior
Chandrakumar Shanmugam 1, Venkat R. Katkoori 1, Nirag C. Jhala 1, William E. Grizzle 1, Gene P. Siegal 1 and Upender Manne 1*
1 Department of Pathology (CS,VRK,NCJ,WEG,GPS,UM) and UAB Comprehensive Cancer Center (WEG,GPS,UM), University of Alabama at Birmingham, Birmingham, Alabama
* To whom correspondence should be addressed. E-mail: manne{at}path.uab.edu.
Submitted on October 9, 2007
Accepted on 20 November 2007
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Abstract |
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For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53nac) 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, p53nac and Bcl-2 expression were significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs which demonstrated p53nac continued to express p53nac in their contiguous CRCs. A similar trend was observed in Bcl-2 expression in that the majority of CAdCs which expressed Bcl-2 continued to express it in their matching CRCs (39 of 44). Patients whose CAdCs and their contiguous CRCs demonstrate p53nac had shorter median survival (35.9 months) than those patients whose CAdCs and CRCs did not (80.56 months). However, patients whose CAdCs had p53nac and lacked Bcl-2 expression had the lowest median survival (15.74 months) when compared to patients whose CAdCs did not demonstrate p53nac but had increased expression of Bcl-2 (71.77 months). These findings suggest that in those adenomas which demonstrate p53nac but lack Bcl-2 expression, their contiguous CRCs are more likely to be aggressive as they progress.
Key Words:
colorectal neoplasia, adenomatous component, p53 nuclear accumulation, Bcl-2 expression