Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012189:Retrospective Studies; D015854:Up-Regulation
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D005819:Genetic Markers; D005472:Fluorouracil