CAM expression in colorectal cancer identifies patients prone to metastasis already in early-stage disease

Introduction: Colorectal cancer continues to be the third most common cancer and constitutes the second leading cause of cancer-associated death among adults in western societies. Despite the improvement of multimodality treatment with surgical resection and chemoradiation, disease recurrence either as local recurrence or metastatic disease represents a major cause of significant cancer-associated morbidity and mortality in colorectal cancer. L1CAM is a stem cell marker and a cell adhesion molecule that can be classified as a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAM). Its aberrant expression in several different types of human solid tumors has been associated with aggressive tumor phenotypes. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer. Methods: A total of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry. Results were correlated with clinicopathological characteristics as well as survival data. Progression-free survival (PFS) and overall survival (OS) were defined as the primary outcomes of this study. Results: L1CAM displayed strong cytoplasmic expression in the colorectal cancer cells. Patients exhibiting high L1CAM expression were associated with advanced disease stage (P < .001), higher T stage (P = .040), the presence of lymph node (P < .001) and distant metastasis (P = .011). No correlations of L1CAM expression were demonstrated with the grade of tumor (P = .647), the presence of vascular (P = .360) or perineural invasion (P = .272) as wells as the presence of mucinous histologic subtype (P = .717). Kaplan-Meier curves revealed a significantly worse 3-year progression-free survival (29.7% vs 87.1%, P < .001) as well worse 5-year overall survival (39.9% vs 87.7%, P < .001) for patients displaying high L1CAM expression. Cox proportional hazard models demonstrated high L1CAM expression, independently of other clinicopathological characteristics, as a prognostic marker of progression-free survival (HR 0.187; 95%CI, 0.075-0.467; P < .001) and overall survival (HR 0.187; 95%CI, 0.049-0.483; P = .001). In the present study, patients with early stage cancer only and high L1CAM expression (Stage I and II according to UICC classification) presented as well significantly worse 3-year progression-free (42.9% vs 91.2%, P = .003) and 5-year overall survival (47.6% vs 90%, P = .008). Conclusion: High L1CAM expression in patients with colorectal cancer is associated with metastatic disease and dismal prognosis even in patients with early-stage disease. L1CAM could either represent a potential target for the development of a tumor profiling test in order to identify patients at high risk for disease recurrence or could be utilized as a target for immunotherapy.