Zusammenfassung
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, 2-microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen ...
Zusammenfassung
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, 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, LMP7, TAP2 and HLA class I were significantly down-regulated in salivary gland carcinomas, whereas 2-microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate KaplanMeier analyses, low expression of LMP7 (P=0.005) and high expression of 2-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. Conclusion 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.
Altmetric