Affiliation:
1. From the Kantonsspital Basel, Departments of Research, Molecular Cancer Research—Oncology, Pathology, and Medical Oncology for the Swiss Group for Clinical Cancer Research (SAKK), Basel; Swiss Group for Clinical Cancer Research (SAKK), Bern; Chirurgische Klinik, Spitalzentrum Biel, Biel; Department of Surgery, Triemlispital Zurich, Switzerland; University of Freiburg, Institute of Molecular Medicine, Freiburg; University of Potsdam, Institute of Biology and Biochemistry, Golm; University of Hamburg,...
Abstract
Purpose: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC.Patients and Methods: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models.Results: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P = .0100) and DFS (HR, 2.00; P = .0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment.Conclusion: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.
Publisher
American Society of Clinical Oncology (ASCO)
Reference66 articles.
1. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule
2. Homotypic and heterotypic Ca++-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface
3. Rojas M, Fuks A, Stanners CP: Biliary glycoprotein, a member of the immunoglobulin supergene family, functions in vitro as a Ca2(+)-dependent intercellular adhesion molecule. Cell Growth Differ 1:527,1990–533,
4. Zhou H, Fuks A, Stanners CP: Specificity of intercellular adhesion mediated by various members of the immunoglobulin supergene family. Cell Growth Differ 1:209,1990–215,
5. Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family.
Cited by
130 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献