摘要目的 研究喉鳞状细胞癌(简称鳞癌)组织中人白细胞抗原(human leucotyte antigen,HLA)Ⅰ类分子和抗原加工递呈(antigen processing machinery,APM)分子抗原转运相关蛋白1(transporter associated with antigen processing,TAP-1)和低分子量蛋白7(low molecular weight polypeptide,LMP-7)下调的频率及其临床意义.方法 用免疫组化方法检测2001-2002年手术切除的51例喉鳞癌组织中HLA-I类抗原重链HLA-ABC和APM分子TAP-1、LMP-7表达情况,并分析其与临床病理特征及预后的关系.结果 HLA-ABC、TAP-1、LMP-7各分子在喉鳞癌组织中的下调率分别是56.9％(29/51)、39.2％(20/51)、45.1％(23/51)；丢失率分别是21.6 ％(11/51)、33.3％(17/51)、27.5％(14/51).HLA-ABC在喉鳞癌组织中的表达分别与TAP-1(r=0.460,P＜0.05)、LMP-7(r=0.685,P＜0.05)的表达呈正相关.在喉鳞癌组织中HLA-ABC、TAP-1、LMP-7的表达均与肿瘤T分期相关(x2值分别为8.61、9.72、8.97,P值均＜0.05),TAP-1、LMP-7的表达分别与肿瘤TNM分期相关(x2值分别为9.18和7.70,P值均＜0.05).单因素分析显示,HLA-ABC阴性表达组与表达下调组、阳性表达组间患者5年累积生存率(cumulative survival rate,CS)及3年无瘤生存率( disease-free survival,DFS)差异有统计学意义(CS组间比较X2值分别为16.18和15.96,DFS组间比较x2值分别为12.54和6.31,P值均＜0.05)；TAP-1阳性表达组与表达下调组、阴性表达组向5年 CS及3年DFS差异有统计学意义(CS组间比较x2值分别为4.23和4.42,DFS组间比较x2值分别为4.12和4.56,P值均＜0.05)；LMP-7阴性表达组与表达下调组、阳性表达组患者5年CS及3年DFS差异有统计学意义(CS组间比较x2值分别为11.46和14.58,DFS组间比较x2值分别为14.17和8.74,P值均＜0.05).多因素分析提示,颈淋巴结转移、复发情况和HLA-ABC表达水平是影响本组喉鳞癌患者预后的重要危险因素(P值均＜ 0.05).结论 喉鳞癌组织中HLA-ABC、TAP-1、LMP-7阴性表达与表达下调不利于肿瘤抗原的递呈及细胞毒性T淋巴细胞向肿瘤实质浸润与杀伤.HLA-Ⅰ类分子、TAP-1、LMP-7阴性表达与表达下调可能促进了癌细胞的发生、侵袭及发展,可能是肿瘤逃避机体免疫监视的方式之一.

abstractsObjective 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. Methods 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.Results HLA class Ⅰ antigens,TAP-1 and LMP-7 expressions were downregulated 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( x2 =8.61,P ＜ 0.05).Both TAP-1 and LMP-7 down-regulations were significantly correlated with T stage ( x2 valueswere 9.72 and 8.97 respectively,P ＜ 0.05 ) and TNM stage( x2 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).Conclusions Down-regulated expressions of HLA class Ⅰ antigen and APM component TAP-1 and LMP-7 occur frequently in laryngeal squamouss 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.