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Expression of CEACAM6 in Resectable Colorectal Cancer: A Factor of Independent Prognostic Significance

Peter Jantscheff, Luigi Terracciano, Adam Lowy, Katharina Glatz-Krieger, Fritz Grunert, Burkhard Micheel, Jens Brümmer, Urs Laffer, Urs Metzger, Richard Herrmann, Christoph Rochlitz

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, University Hospital Eppendorf, Hamburg, Germany.

Address reprint requests to Peter Jantscheff, PhD, Albert-Ludwigs-University of Freiburg, Department of Experimental Urology, Stefan-Meier-Str 8, D-79104 Freiburg/Br, Germany; e-mail: jape{at}sun11.ukl.uni-freiburg.de.

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.

Supported by the Foundation for Clinical Cancer Research, Department of Oncology, Kantonsspital Basel, and by the Krebsliga Beider Basel, Basel, Switzerland. P.J., L.T., and A.L. contributed equally to this work.

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