中华耳鼻咽喉头颈外科杂志
中華耳鼻嚥喉頭頸外科雜誌
중화이비인후두경외과잡지
CHINESE JOURNAL OF OTORHINOLARYNGOLOGY HEAD AND NECK SURGERY
2012年
3期
234-240
,共7页
曾泉%王晓雷%徐震纲%吕宁%郑闪%赵清正%唐平章
曾泉%王曉雷%徐震綱%呂寧%鄭閃%趙清正%唐平章
증천%왕효뢰%서진강%려저%정섬%조청정%당평장
癌,鳞状细胞%喉肿瘤%HLA抗原%抗原呈递
癌,鱗狀細胞%喉腫瘤%HLA抗原%抗原呈遞
암,린상세포%후종류%HLA항원%항원정체
Carcinoma,squamous cell%Laryngeal neoplasms%HLA antigens%Antigen presentation
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.
目的 研究喉鱗狀細胞癌(簡稱鱗癌)組織中人白細胞抗原(human leucotyte antigen,HLA)Ⅰ類分子和抗原加工遞呈(antigen processing machinery,APM)分子抗原轉運相關蛋白1(transporter associated with antigen processing,TAP-1)和低分子量蛋白7(low molecular weight polypeptide,LMP-7)下調的頻率及其臨床意義.方法 用免疫組化方法檢測2001-2002年手術切除的51例喉鱗癌組織中HLA-I類抗原重鏈HLA-ABC和APM分子TAP-1、LMP-7錶達情況,併分析其與臨床病理特徵及預後的關繫.結果 HLA-ABC、TAP-1、LMP-7各分子在喉鱗癌組織中的下調率分彆是56.9％(29/51)、39.2％(20/51)、45.1％(23/51)；丟失率分彆是21.6 ％(11/51)、33.3％(17/51)、27.5％(14/51).HLA-ABC在喉鱗癌組織中的錶達分彆與TAP-1(r=0.460,P＜0.05)、LMP-7(r=0.685,P＜0.05)的錶達呈正相關.在喉鱗癌組織中HLA-ABC、TAP-1、LMP-7的錶達均與腫瘤T分期相關(x2值分彆為8.61、9.72、8.97,P值均＜0.05),TAP-1、LMP-7的錶達分彆與腫瘤TNM分期相關(x2值分彆為9.18和7.70,P值均＜0.05).單因素分析顯示,HLA-ABC陰性錶達組與錶達下調組、暘性錶達組間患者5年纍積生存率(cumulative survival rate,CS)及3年無瘤生存率( disease-free survival,DFS)差異有統計學意義(CS組間比較X2值分彆為16.18和15.96,DFS組間比較x2值分彆為12.54和6.31,P值均＜0.05)；TAP-1暘性錶達組與錶達下調組、陰性錶達組嚮5年 CS及3年DFS差異有統計學意義(CS組間比較x2值分彆為4.23和4.42,DFS組間比較x2值分彆為4.12和4.56,P值均＜0.05)；LMP-7陰性錶達組與錶達下調組、暘性錶達組患者5年CS及3年DFS差異有統計學意義(CS組間比較x2值分彆為11.46和14.58,DFS組間比較x2值分彆為14.17和8.74,P值均＜0.05).多因素分析提示,頸淋巴結轉移、複髮情況和HLA-ABC錶達水平是影響本組喉鱗癌患者預後的重要危險因素(P值均＜ 0.05).結論 喉鱗癌組織中HLA-ABC、TAP-1、LMP-7陰性錶達與錶達下調不利于腫瘤抗原的遞呈及細胞毒性T淋巴細胞嚮腫瘤實質浸潤與殺傷.HLA-Ⅰ類分子、TAP-1、LMP-7陰性錶達與錶達下調可能促進瞭癌細胞的髮生、侵襲及髮展,可能是腫瘤逃避機體免疫鑑視的方式之一.
목적 연구후린상세포암(간칭린암)조직중인백세포항원(human leucotyte antigen,HLA)Ⅰ류분자화항원가공체정(antigen processing machinery,APM)분자항원전운상관단백1(transporter associated with antigen processing,TAP-1)화저분자량단백7(low molecular weight polypeptide,LMP-7)하조적빈솔급기림상의의.방법 용면역조화방법검측2001-2002년수술절제적51례후린암조직중HLA-I류항원중련HLA-ABC화APM분자TAP-1、LMP-7표체정황,병분석기여림상병리특정급예후적관계.결과 HLA-ABC、TAP-1、LMP-7각분자재후린암조직중적하조솔분별시56.9％(29/51)、39.2％(20/51)、45.1％(23/51)；주실솔분별시21.6 ％(11/51)、33.3％(17/51)、27.5％(14/51).HLA-ABC재후린암조직중적표체분별여TAP-1(r=0.460,P＜0.05)、LMP-7(r=0.685,P＜0.05)적표체정정상관.재후린암조직중HLA-ABC、TAP-1、LMP-7적표체균여종류T분기상관(x2치분별위8.61、9.72、8.97,P치균＜0.05),TAP-1、LMP-7적표체분별여종류TNM분기상관(x2치분별위9.18화7.70,P치균＜0.05).단인소분석현시,HLA-ABC음성표체조여표체하조조、양성표체조간환자5년루적생존솔(cumulative survival rate,CS)급3년무류생존솔( disease-free survival,DFS)차이유통계학의의(CS조간비교X2치분별위16.18화15.96,DFS조간비교x2치분별위12.54화6.31,P치균＜0.05)；TAP-1양성표체조여표체하조조、음성표체조향5년 CS급3년DFS차이유통계학의의(CS조간비교x2치분별위4.23화4.42,DFS조간비교x2치분별위4.12화4.56,P치균＜0.05)；LMP-7음성표체조여표체하조조、양성표체조환자5년CS급3년DFS차이유통계학의의(CS조간비교x2치분별위11.46화14.58,DFS조간비교x2치분별위14.17화8.74,P치균＜0.05).다인소분석제시,경림파결전이、복발정황화HLA-ABC표체수평시영향본조후린암환자예후적중요위험인소(P치균＜ 0.05).결론 후린암조직중HLA-ABC、TAP-1、LMP-7음성표체여표체하조불리우종류항원적체정급세포독성T림파세포향종류실질침윤여살상.HLA-Ⅰ류분자、TAP-1、LMP-7음성표체여표체하조가능촉진료암세포적발생、침습급발전,가능시종류도피궤체면역감시적방식지일.
Objective 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.
