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The prognostic impact of human leukocyte antigen ( HLA ) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases
Author(s) -
Müller Maximilian,
Agaimy Abbas,
Zenk Johannes,
Ettl Tobias,
Iro Heinrich,
Hartmann Arndt,
Seliger Barbara,
Schwarz Stephan
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12086
Subject(s) - calreticulin , calnexin , human leukocyte antigen , antigen , beta 2 microglobulin , salivary gland , antigen processing , biology , medicine , immunology , endocrinology , endoplasmic reticulum , major histocompatibility complex , mhc class i , microbiology and biotechnology
Aims 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 ). Methods and results Protein expression of human leukocyte antigen ( HLA )‐A, heavy chain ( HC )‐10, β 2 ‐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, LMP 7, TAP 2 and HLA class I were significantly down‐regulated in salivary gland carcinomas, whereas β 2 ‐microglobulin, calnexin, LMP 2, and TAP 1 were upregulated. Expression of calreticulin, ER p57 and tapasin was unaltered. In univariate Kaplan–Meier analyses, low expression of LMP 7 ( P = 0.005) and high expression of β 2 ‐microglobulin ( P = 0.028), HLA ‐A ( P < 0.001), TAP 1 ( 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), LMP 7 ( 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. Conclusion The prognostic influence of up‐regulated HLA ‐A and tapasin and down‐regulated LMP 7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas.