title: Absence or low IGF-1R-expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection.
abstract: OBJECTIVE
  Esophageal adenocarcinoma (EAC) incidence increases, maybe due to increasing prevalences of obesity and diabetes. Concurrent hyperinsulinemia might promote carcinogenesis via the insulin-like growth factor-I receptor (IGF-1R). Expression of the IGF-1R was studied in correlation with diabetes and prognostic parameters.
  
  
  METHODS
  Patients with EAC undergoing esophagectomy were prospectively selected. From resected tumors a tissue microarray was constructed. Immunohistochemistry evaluated IGF-1R-expression. Logistic-, cox regression models and survival analyses assessed if diabetes and IGF-1R-expression were associated with prognostic parameters. IGF-1R-expression in normal and Barrett tissues was studied.
  
  
  RESULTS
  Absence or low IGF-1R-expression was associated with T3-, grade 3 tumors and R1 resections (P = 0.001, P = 0.025, P < 0.001, respectively). Logistic regression showed that this was associated with R1 resections (HR 0.24, 95%CI 0.11-0.52). Diabetes was not associated with IGF-1R-expression (P = 0.612). Absence or low IGF-1R-expression decreased 5-year overall survival (P = 0.023) univariably, but not multivariably. IGF-1R-expression was present in Barrett tissues, but diminished in high-grade dysplasia.
  
  
  CONCLUSIONS
  Absence or low expression of IGF-1R was associated with high grade- and advanced tumors and less radical resections. IGF-1R might be a tumor marker in Barrett's esophagus since a change in expression patterns was found in the course from normal esophageal tissue to adenocarcinoma.
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Kirstin
authors.initials: K
authors.lastname: De Bruijn
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joel
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Fadime
authors.initials: F
authors.lastname: Dogan
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: Spaander
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joseph
authors.initials: J
authors.lastname: Janssen
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Wijnhoven
authors.affiliation: Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Borsboom
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Hofland
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Casper
authors.initials: C
authors.lastname: van Eijck
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1
keywords: Barrett's esophagus; diabetes mellitus; esophageal adenocarcinoma; insulin-like growth factor-1-receptor expression; prognostic parameters; survival