Abstracts
2002 Digestive Disease Week

# 101353 Abstract ID: 101353 Cooperative Effect of IGF1-R and Src Protein Expression in Barrett's Neoplasia
Scott T Kelley, Domenico Coppolla, Hongquan Zhan, Jin Cheng, Richard Jove, Richard C Karl, Tampa, FL

Background: Several changes in gene expression have been shown to occur as Barrett's epithelium progresses from intestinal metaplasia to dysplasia and carcinoma. Recent studies have implicated c-Src protein kinase as a regulator of tumor growth and progression of Barrett's associated neoplasia (BAN). It has also been shown that an activated Src is capable of inducing overexpression of insulin-like growth factor 1 receptor (IGF1-R) on tumor cells. We postulated that the expression of insulin-like growth factor 1 receptor (IGF1-R) should correlate with c-Src expression and progression of Barrett's neoplasia to carcinoma. Methods: To study modifications in IGF1-R, and c-Src protein expression during the progression of BAN, we analyzed 44 resected gastro-esophagectomy specimens by immunohistochemistry using antibodies to human IGF1-R, c-Src. In a subset of these tumors, the Src immunohistochemical results were matched to Western blot and Kinase assays. Results: Twenty-two of the cases showed intestinal metaplasia, 25 low grade dysplasia, 28 high grade dysplasia, 34 invasive adenocarcinoma, and 19 lymph node metastasis. Strong IGF1-R membranous staining and strong c-Src expression were identified as seen in table 1. Unpaired t-test showed no difference between immunohistochemical markers within each condition.Western blot and Kinase assays confirmed the Src immunohistochemical results. Conclusion: Our data indicate that expression levels of IGF1-R, and c-Src proteins are coordinately elevated during the progression of Barrett's associated neoplasia to adenocarcinoma. These findings are consistent with important roles of these growth regulatory proteins in the development of cancers associated with Barrett's epithelium. The activation of c-Src may induce esophageal metaplastic cells to progress to dysplasia and carcinoma by increasing the expression of insulin-like growth factor 1 receptor on their surface, implying that receptor directed intervention might interrupt this progression to malignancy.