title: ALCAM (CD166) expression and serum levels are markers for poor survival of esophageal cancer patients.
abstract: The expression of the activated leukocyte cell adhesion molecule (ALCAM and CD166) is increased in various types of cancer. We aimed to evaluate its role as a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM expression in 299 primary lesions, 147 lymph node and 46 distant metastases from EC patients, on a tissue microarray using immunohistochemistry. Bone marrow samples from representative cancer patients (n = 16), taken before primary surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph node 76% and distant metastases 80%). ALCAM expression was not associated with histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive patients had significantly worse recurrence-free and overall survival (OS; p = 0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes, ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM expression and elevated s-ALCAM serum values are powerful prognostic variables for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The results of our study provide preliminary evidence for the potential clinical utility of ALCAM as a prognostic biomarker for EC, which might be a basis for future clinical application. In addition, ALCAM expression in a subset of DTC of the bone marrow indicates a potential function in the metastatic cascade of EC.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany. mtachezy@uke.uni-hamburg.de
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger
authors.forename: Hilke
authors.initials: H
authors.lastname: Zander
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Florian
authors.initials: F
authors.lastname: Gebauer
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000097:blood* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D040081:Protein Array Analysis; D012189:Retrospective Studies
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D014408:Biomarkers, Tumor; D007633:Keratins