title: Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer.
abstract: BACKGROUND
  Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC.
  
  
  METHODS
  MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival.
  
  
  RESULTS
  BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4(+) and CD8(+)) and macrophages.
  
  
  CONCLUSIONS
  Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goeppert
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Frauenschuh
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roessler
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Hafezi
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Renner
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.|National Center for Tumour Diseases (NCT), Heidelberg D-69120, Germany.|Institute of Pathology, Technical University Munich D-81675, Munich, Germany.|German Cancer Consortium (DKTK).
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001659:Biliary Tract / Q000276:immunology* / Q000473:pathology; D005260:Female; D005706:Gallbladder Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D015395:Histocompatibility Antigens Class I