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[523] Progressive Increase in PPM1D/wip-1 Protein Expression in Normal Mucosa, Tubular Adenoma, and Low- and High-Grade Colorectal Adenocarcinoma
DP Hartmann, BVS Kallakury, J Luka, EA Apella, N Azumi. Georgetown University Hospital, Washington, DC; Bioworld Consulting Labs, New Windsor, MD; NIH, Bethesda, MD
Background: The protein encoded by the PPM1D/wip-1 gene is a member of the PP2C family of Ser/Thr protein phosphatase which down-regulates the apoptotic activity of p53. We have previously reported the correlation of wip-1 over-expression with higher stage, higher grade and the presence of lymph node metastasis in colorectal carcinoma.
Design: Using a novel monoclonal antibody to wip-1(Bioworld), a tissue microarray of formalin-fixed tissue consisting of 34 normal colonic mucosa, 26 tubular adenomas, 23 low-grade and 19 high-grade colorectal adenocarcinomas was tested for wip-1 expression immunohistochemically to further elucidate the correlation of protein expression and progression of colorectal carcinogenesis. Staining was scored on a scale of 0-3+, based on intensity and percentage of positive cells.
Results: Immunoreactivity for wip-1 protein was exclusively intranuclear and was seen in 4/34 (12%) normal mucosa, 26/26 (100%) adenomas and 42/42 (100%) carcinomas . However, only 6/26 adenomas (23%) showed 2+ as compared to 34/42 (81%) carcinomas showed 2+ or 3+. There was no statistical difference in wip-1 positvity between low and high grade carcinomas.
Tubular Adenomas| Staining | 0 | 1+ | 2+ | 3+ | | Sample# | 0 | 20 | 6 | 0 |
Adenocarcinomas| Staining | 0 | 1+ | 2+ | 3+ | | Sample# | 0 | 8 | 31 | 3 |
Conclusions: Expression of wip-1 progressively increases from normal mucosa to neoplastic lesions suggesting its role in the carcinogenesis. wip-1 appears as early carcinogenic event in formation of adenomas and, then, the expression intensifies as adenomas progress to carcinomas. These results also support wip-1 as a potential therapeutic target in the treatment of carcinomas of colon and other organs.
Category: Gastrointestinal
Tuesday, March 27, 2007
Poster # 41, Tuesday Afternoon
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