title: The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer.
abstract: The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-G]) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 4H84 (anti-HLA-G), beta2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage > or = II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on disease-specific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.
authors.affiliation: Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Claudia B M
authors.initials: CB
authors.lastname: Bijen
authors.forename: Enja J
authors.initials: EJ
authors.lastname: Bantema-Joppe
authors.forename: Renske A
authors.initials: RA
authors.lastname: de Jong
authors.forename: Ninke
authors.initials: N
authors.lastname: Leffers
authors.forename: Marian J E
authors.initials: MJ
authors.lastname: Mourits
authors.forename: Henk F
authors.initials: HF
authors.lastname: Eggink
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis*; D015234:HLA-A Antigens / Q000096:biosynthesis; D015235:HLA-B Antigens / Q000096:biosynthesis; D015236:HLA-C Antigens / Q000096:biosynthesis; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis; D001613:beta 2-Microglobulin / Q000096:biosynthesis
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin