喉鳞状细胞癌组织中人白细胞Ⅰ类分子和抗原加工递呈分子的表达

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

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。

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.