Overexpression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Gastrointestinal Dsyplasia and Adenocarcinoma
K Gilbert-Lewis, J Heitzman, W Feng, W Li. University of Texas Health Science Center at Houston, Houston, TX
Background: X-linked inhibitor of apoptosis (XIAP) is a human inhibitor of apoptosis protein involved in the blockage of intrinsic and extrinsic apoptotic pathways. XIAP has been implicated in cancer metastasis and progression in a variety of neoplasms. The aim of this study is to determine the expression pattern of XIAP in gastric and colorectal carcinoma and correlate its expression with clinicopathologic variables.
Design: Formalin-fixed paraffin-embedded tissue sections of 18 cases of gastric adenocarcinoma and 28 cases of colorectal carcinoma were immunostained for XIAP using standard avidin-biotin techniques. The level of XIAP expression was categorized into four grades: 0 (negative), 1+ (weak), 2+ (moderate), or 3+ (strong) based on intensity of staining.
Results: There was significantly higher expression of XIAP in the neoplastic areas compared to normal matched tissue, independent of tumor grade in 18 cases of gastric adenocarcinoma and 28 cases of colorectal carcinoma. All tumor cells were moderate to strongly positive, with an average staining intensity grade of 2.8±0.3 compared to normal epithelium that stained weakly with an average grade 1.1±0.5. Areas with dysplastic epithelium displayed similar XIAP staining to neoplastic areas. The results show significant XIAP over-expression in neoplastic tissue compared to normal matched epithelium (p<0.0001).
Conclusions: Significant over-expression of XIAP in gastrointestinal adenocarcinomas suggests XIAP as an integral role in the spectrum of tumor progression. While normal epithelium retains the low-level expression of XIAP in an effort to maintain homeostasis or avoid inappropriate cell death, dysplastic epithelium and adenocarcinomatous cells fail to turn off XIAP signals. The up-regulation of XIAP expression suggests its possible role in gastric and colorectal carcinogenesis and its potential utility as a target for innovative therapy.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 67, Tuesday Afternoon