目的研究喉鳞状细胞癌(简称鳞癌)组织中人白细胞抗原(human leueotyte antigen,HLA)Ⅰ类分子和抗原加工递呈(antige nprocessing 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 weightpolypeptide,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一1、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(X^2。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(X^2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-freesurvival,DFS)差异有统计学意义(cs组间比较x。值分别为16.18和15.96,DFS组间比较X。值分别为12.54和6.31,P值均〈0.05);TAP一1阳性表达组与表达下调组、阴性表达组问5年cs及3年DFS差异有统计学意义(cs组问比较X^2值分别为4.23和4.42,DFS组间比较)(2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x。值分别为14.17和8.74,P值均〈0.05)。多因素分析?
Objective To investigate the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regnlation 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 antigenprocessing (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 down- regulated in 56. 9% (29/51), 39.2 % (20/51) and 45.1% (23/51) of the tested specimens respectively, whereas HLA class 1 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 values were 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-l, LMP-7 and HLA class I antigen down-regulations were significantly associated with reduced patients' overall survival ( P 〈 0. 05 ) arid disease-free survival ( P 〈 0. 05 ). Multivariate analysis showed lymph node metastasis, recurrence and HLA classⅠantigen down-regulation were unfavorable prognostic factors(P 〈 0. 05). Conclusions Down-regulated expressions of HLA classⅠ 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 turnout progression and mortality.