Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in laryngeal squamous cell carcinoma

Abstract

To investigate the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) and to assess the clinical significance of these defects. Fifty-one formalin-fixed, paraffin-embedded SCC specimens were examined for the expressions of APM component transporter associated with antigen processing (TAP1) and low molecular weight polypeptide (LMP-7) and HLA class I antigen by immunohistochemistry. HLA class I antigens, TAP-1 and LMP-7 expressions were down-regulated in 56.9% (29/51), 39.2% (20/51) and 45.1% (23/51) of the tested specimens respectively, whereas HLA class I antigens, TAP-1 and LMP-7 expressions lost in 21.6% (11/51), 33.3% (17/51) and 27.5% (14/51) of the tested specimens respectively. TAP-1 and LMP-7 expressions were significantly correlated with HLA class I antigen expression (r=0.460, P<0.05 and r=0.685, P<0.05, respectively). HLA class I antigens down-regulation was significantly correlated with T stage (χ2=8.61, P<0.05). Both TAP-1 and LMP-7 down-regulations were significantly correlated with T stage (χ2 values were 9.72 and 8.97 respectively, P<0.05) and TNM stage (χ2 values were 9.18 and 7.70 respectively, P<0.05). TAP-1, LMP-7 and HLA class I antigen down-regulations were significantly associated with reduced patients' overall survival (P<0.05) and disease-free survival (P<0.05). Multivariate analysis showed lymph node metastasis, recurrence and HLA class I antigen down-regulation were unfavorable prognostic factors (P<0.05). Down-regulated expressions of HLA class I antigen and APM component TAP-1 and LMP-7 occur frequently in laryngeal squamous cell carcinoma, by which cancer cells could avoid immune surveillance, while HLA class I antigen down-regulation is a major contributing factor to tumour progression and mortality.