1999 Abstract: 2083 MDM2/P53 PROTEIN EXPRESSION IN THE DEVELOPMENT OF COLORECTAL ADENOCARCINOMA.
Abstracts
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The murine double minute 2 (MDM2) oncoprotein inhibits p53-mediated tumor suppression. MDM2 has been shown to be overexpressed in sarcomas and more recently, was implicated in the pathogenesis of carcinomas. PURPOSE: To determine the expression pattern of MDM2 in adenomas, and colorectal adenocarcinomas (CRC) and whether there is a correlation between MDM2 and p53 protein status. METHODS: Paraffin-embedded tissues from 52 cases of CRC, and their adjacent normal tissue (N-CRC), as well as 56 sporadic adenomas, were investigated for the immunohistochemical (IHC) expression of MDMD2 and p 53 proteins RESULTS: Immunoreactivity of p53 indicating p53 gene mutation (p53+), was significantly higher in CRC (44%) compared to adenomas (23.2%) (p <0.01, Chi-square). None of the N-CRC expressed the immunoreactive p53 protein. MDM2 overexpression (MDM2+) was similar in adenomas (30.3%) and CRC (25%) but only 2 out of 52 N-CRC (3.8%) showed overexpression of MDM2. In most cases, MDM2 expression was associated with negative p53 expression (wild-type p53) in both adenomas (r = 0.59, P <0.001, linear regression analysis) and in CRC (r = 0.69, p <0.0001). No correlation was found between MDM2, p53 expression and either of the histological grade, nodal status or the location of the tumors. CONCLUSIONS: There is higher p53 mutation in the CRC compared to adenomas and N-CRC. The data indicate that MDM2 is overexpressed in CRC and is significantly associated with the wild-type p53 compared to the N-CRC of the same patient. MDM2 expression pattern is similar in adenomas and CRC, which may suggest that MDM2 overexpression is an early event in the progression of CRC. Copyright 1996 - 1999, SSAT, Inc. |