title: The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases.
abstract: OBJECTIVE
  To study abnormalities of proteins of the major histocompatibility complex class I in a series of 288 salivary gland carcinomas, and to correlate findings with patients' overall survival (OS).
  
  
  RESULTS
  Protein expression of human leukocyte antigen (HLA)-A, heavy chain (HC)-10, β2 -microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen processing (TAP) 1 and 2, calnexin, calreticulin, endoplasmic reticulum (ER) p57 and tapasin was evaluated by immunohistochemistry and semiquantitatively analyzed. As compared with normal salivary gland tissue, HLA-A, LMP7, TAP2 and HLA class I were significantly down-regulated in salivary gland carcinomas, whereas β2 -microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate Kaplan-Meier analyses, low expression of LMP7 (P = 0.005) and high expression of β2 -microglobulin (P = 0.028), HLA-A (P < 0.001), TAP1 (P = 0.01), and tapasin (P < 0.001) were significantly associated with shorter OS. In multivariate analysis incorporating tumour stage, nodal/distant metastasis, and grade, HLA-A (P = 0.014), LMP7 (P = 0.033), and tapasin (P = 0.024), as well as distant metastasis (P = 0.012) and high tumour grade (P < 0.001), remained statistically significant.
  
  
  CONCLUSIONS
  The prognostic influence of up-regulated HLA-A and tapasin and down-regulated LMP7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas.
authors.affiliation: Department of Pathology, University of Erlangen, Erlangen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Müller
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Johannes
authors.initials: J
authors.lastname: Zenk
authors.forename: Tobias
authors.initials: T
authors.lastname: Ettl
authors.forename: Heinrich
authors.initials: H
authors.lastname: Iro
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D037281:Calnexin / Q000378:metabolism; D002648:Child; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005260:Female; D015234:HLA-A Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000276:immunology* / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015234:HLA-A Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; D037281:Calnexin; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex