title: Loss of anterior gradient-2 expression is an independent prognostic factor in colorectal carcinomas.
abstract: OBJECTIVE
  The human Anterior Gradient-2 (AGR2) protein is strongly expressed in various human cancers, and it has been described to promote aggressive tumour features in some entities. So far, a comprehensive analysis of AGR2 expression in colorectal carcinomas has not been described.
  
  
  METHODS
  Normal intestinal cells and colorectal carcinoma cell lines were analysed for AGR2 expression. AGR2 protein expression was immunohistochemically analysed in 28 normal tissue samples and 1068 tissue samples of clinically well characterised colorectal carcinomas. For statistical analysis, chi square test, spearman rank correlations, Kaplan-Meier estimates (Log rank test) and Cox regression were applied to test for diagnostic or prognostic associations.
  
  
  RESULTS
  In the normal intestinal cell line and in normal colon mucosa AGR2 was found in all cases (n=28). In contrast, loss of AGR2 was found in all six analysed colorectal cancer cell lines and in 833/1068 (78%) of the colorectal carcinoma tissue samples analysed, and it was significantly associated with a higher tumour grade and tumour localisation in the left-sided colon. In addition to the conventional prognostic tumour parameters pT category, nodal status, metastasis and histological tumour grade the loss of AGR2 expression was significantly associated with reduced overall survival times in univariate and multivariate analyses, thus suggesting AGR2 as an independent prognostic factor in primary colorectal carcinoma.
  
  
  CONCLUSIONS
  AGR2 is frequently lost in colorectal carcinomas and might be a novel independent prognostic factor for overall patient survival.
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Germany.
authors.forename: Marc-Oliver
authors.initials: MO
authors.lastname: Riener
authors.affiliation: Institute of Pathology, University Hospital Bonn, Germany.
authors.forename: Thore
authors.initials: T
authors.lastname: Thiesler
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Amann
authors.affiliation: Cantonal Institute for Pathology, Cantonal Hospital Liestal, Switzerland.
authors.forename: Gieri
authors.initials: G
authors.lastname: Cathomas
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Switzerland.
authors.forename: Florian Rudolph
authors.initials: FR
authors.lastname: Fritzsche
authors.affiliation: Institute of Pathology, University Hospital Aachen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
authors.affiliation: Department of Visceral Surgery, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.affiliation: Institute of Pathology, University of Heidelberg, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Institute of Pathology, University Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Institute of Pathology, University Hospital Bonn, Germany. Electronic address: Glen.Kristiansen@ukb.uni-bonn.de.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009088:Mucoproteins; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015513:Oncogene Proteins; D016016:Proportional Hazards Models; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D055815:Young Adult
chemical_list: C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins
keywords: AGR2; Colorectal carcinoma; Immunohistochemistry; Prognosis