Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a negative regulator of tumor cell growth, and may function as a tumor suppressor. CEACAM1 expression is down-regulated with increasing histologic grade in a number of malignancies. The authors hypothesized that loss of CEACAM1 expression in hepatocellular carcinoma (HCC) cells may function as an adverse prognostic factor.
Methods: A retrospective analysis was conducted of 139 consecutive patients who underwent resection for HCC, with a median follow-up period of 83 months. Immunohistochemistry of the resected specimens was conducted using a monoclonal anti-CEACAM1 antibody. CEACAM1 expression in HCC was classified into two categories: diffuse expression, characterized by positive staining throughout the tumor specimen, or loss of expression, in which there were distinct areas of negative staining within the tumor specimen.
Results: Of the 139 patients, 113 were classified as having tumors with diffuse expression and 26 had loss-of-expression tumors. Loss of CEACAM1 expression was more frequent in tumor specimens with Edmondson-Steiner Grades III or IV (21 of 32 [66%]) than in tumor specimens with Grades I or II (5 of 107 [5%]; P < 0.001) and was always seen in areas with the highest histologic grade. Loss of CEACAM1 expression was significantly associated with large tumor size, multiplicity of the tumor, portal vein invasion, and satellite nodules and affected survival adversely, according to univariate (P < 0.0001) and multivariate analyses (relative risk, 5.737; P < 0.001).
Conclusions: Loss of CEACAM1 expression reflects aggressive tumor biology and thus indicates a poor prognosis for patients with HCC.