Changes in expression pattern of CEACAM1 in esophageal cancer: A factor of independent prognostic significance

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3028 Purpose: Carcinoembryonatic antigen-related-cell adhesion molecule 1 (CEACAM1) has recently been implicated in cancer development and progression. This study was performed to evaluate the prognostic relevance of CEACAM1 expression in esophageal cancer. Experimental design: Immunhistochemical analysis using the monoclonal anti-CEACAM1-antibody 4D1/C2 was performed in a tissue microarray (TMA) constructed from paraffin-embedded tissues of patients with primary tumors (n=248), and matched nodal (n=145) as well as distant (n=45) metastases of the esophagus who underwent surgery between 1994 and 2004. Results: CEACAM1 expression was detected in 141 of 248 (57%) esophageal cancers. Staining intensity was considered strong in 104 (74 %), and weak in 37 (26%) of the primary tumors. CEACAM1 expression findings of lymph node and distant metastases were strongly linked to the CEACAM1 findings in the respective primary tumors. CEACAM1 expression level was unrelated to patient survival. However, the staining pattern was prognostically relevant. Patients with apical expression (staining limited to the luminal surface of the cells) had a significant better overall survival (p=0.0076) as compared to tumors with a membranous pattern (staining surrounding the cells). Remarkably, the prognostic relevance of the staining pattern was linked to adenocarcinomas (p=0.0004), where it was independent from tumor stage (p=0.0064 in the subset of pT3-4 cancers), nodal stage (p=0.0032 in the subset of pN1) and grade (p=0.0286 in the subset of G3). In the subset of squamous cell carcinomas, apical expression pattern was not observed. In a multivariate Cox regression analysis including sex, age, tumor stage, differentiation grade and nodal status as covariates, next to tumor stage and nodal status, only the CEACAM1 expression pattern was a significant prognostic factor for survival (p =0.0112). Conclusion: Loss of the physiological apical expression pattern of CEACAM1 is linked to poor prognosis in esophageal cancer. This change of the expression pattern might be useful to stratify patients with adenocarcinomas of the esophagus into low-risk and high-risk groups.