L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer

Abstract

L1, a new target gene for Wnt/beta-catenin-TCF signaling, has been identified in the invasive front of colorectal cancer cells in vitro study. The L1 molecule is localized on the cell surface in tumor tissues, accompanied with loss of beta-catenin and E-cadherin. However, such association between L1 expression and prognosis of colorectal cancer has not yet been investigated in clinical study. We investigated the expression of L1, E-cadherin, and beta-catenin in tumor cells to determine correlations between the clinicopathologic characteristics and the expression of these molecules and to evaluate the efficacy of the use of these molecules as prognostic markers for patient survival. We investigated 138 patients who received diagnoses of colorectal cancer and who underwent surgery between January 1995 and December 2000 at the Korea University Hospital. Tissues were obtained from paraffin-embedded blocks of the tumors and studied by tissue microarray analysis. Immunohistochemical staining for L1, beta-catenin, and E-cadherin was performed for each specimen. L1 expression was found to be correlated with advanced cancer stage (P = .001), distant metastasis (P < .001), and tumor recurrence (P = .006). Survival analysis showed that reduced expression of beta-catenin and E-cadherin, and expression of L1 were statistically significantly related to poor survival. Multivariate analysis revealed that L1 expression was an independent prognostic factor for patient survival. L1 expression is associated with tumor progression and poor survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.