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Proffered Abstract (Plenary Session): Determinants of Patient Prognosis

REG1Aand its receptor EXTL3 are prognostic markers in colorectal cancer

Max-Delbrueck Center, Berlin, Germany

Abstract

PR-7

Purpose: By microarray screening for genes with prognostic relevance in colorectal cancer, we found Regenerating Islet-Derived 1 Alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REG1A expression was quantified in a colorectal cancer patient cohort by Taqman PCR and localized by tissue microarray based in-situ hybridization. Simultaneously, expression of REG1A receptor Exostoses (Multiple)-Like 3 (EXTL3) was assessed.Experimental Design: Tumor and normal tissue from 63 nonpretreated colorectal cancer patients were analyzed with respect to REG1A expression by quantitative real-time PCR. Additionally, 31 mucosa biopsies from healthy individuals and 22 adenomas were included. Tissue microarray was constructed with tumor and normal tissue samples from 42 colorectal cancer patients. EXTL3 expression was determined in 56 individuals by Taqman PCR.Results: REG1A was significantly upregulated in tumor specimens, and in adenoma (p = 0.005) vs normal tissue (p < 0.005) as compared to healthy colorectal tissue. Gene expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.005). Moreover, REG1A turned out to be a significant predictor of disease free survival (p < 0.05). By insitu hybridization it was verified to be confined to the crypt epithelium. Similarly, EXTL3 displayed a tendency of upregulation in peritoneal carcinomatosis and could be successfully exploited for predicting patient outcome (p < 0.05). Conclusions: We present evidence that REG1A and its receptor EXTL3 are markers of prognostic value in colorectal cancer. Furthermore, our data suggest that REG1A and EXTL3 are associated with peritoneal carcinomatosis.