Abstracts
1999 Digestive Disease Week

# 2083 MDM2/P53 PROTEIN EXPRESSION IN THE DEVELOPMENT OF COLORECTAL ADENOCARCINOMA.
G Abdel-Fattah, B Yoffe, B Krishnan, V Khaoustov, Baylor Coll of Medicine, Houston, TX; Kamal Itani, Baylor Coll of Medicine and VAMC (112A), Houston, TX

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.

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