Head and Neck Cancer Center, Hokuto Hospital, Hokkaido 080-0833, Japan.
Oncol Rep. 2010 Apr;23(4):933-9. doi: 10.3892/or_00000717.
HLA class I antigen processing machinery plays a crucial role in the generation of peptides from endogeneously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The purpose of this study was to analyze the downregulation of HLA class I antigen, transporter associated with antigen processing (TAP) and tapasin in primary and metastatic lesions of head and neck squamous cell carcinoma (HNSCC) and to compare TAP, tapasin and HLA class I antigen downregulation in metastatic lesions with that of primary lesions. We analyzed expression levels of TAP1, TAP2, tapasin and HLA class I antigen in 25 primary and autologous metastatic lesions by staining formalin-fixed, paraffin-embedded tissue sections in the immunoperoxidase reaction. We identified the expression levels of TAP1, TAP2, tapasin and HLA class I antigen were coordinately downregulated in both primary and metastatic lesions and were significantly lower in metastatic lesions than in autologous primary lesions tested. HLA class I antigen downregulation in metastatic lesion was significantly associated with reduced disease-free survival of patients (P<0.05). Multivariate Cox proportional hazards model analysis identified negativity of HLA class I antigen as an independent prognostic marker. HLA class I antigen and TAP are likely to be downregulated in metastatic lesions compared with primary lesions in HNSCC. The higher frequency of HLA class I antigen and TAP down-regulation in metastases play a role in the clinical course of the disease.
HLA I 类抗原加工机制在从内源性合成蛋白生成肽段以及将其呈递给细胞毒性 T 淋巴细胞方面发挥着关键作用。本研究旨在分析头颈部鳞状细胞癌(HNSCC)原发和转移病灶中 HLA I 类抗原、抗原加工相关转运体(TAP)和 tapasin 的下调,并比较转移病灶与原发病灶中 TAP、tapasin 和 HLA I 类抗原下调的情况。我们通过免疫过氧化物酶反应对 25 例福尔马林固定、石蜡包埋的组织切片进行染色,分析了 TAP1、TAP2、tapasin 和 HLA I 类抗原在 25 例原发和自体转移病灶中的表达水平。我们发现 TAP1、TAP2、tapasin 和 HLA I 类抗原的表达水平在原发和转移病灶中均呈协同下调,且转移病灶中的表达水平明显低于自体原发病灶。HLA I 类抗原下调与患者无病生存期显著相关(P<0.05)。多变量 Cox 比例风险模型分析确定 HLA I 类抗原阴性为独立的预后标志物。与 HNSCC 的原发病灶相比,转移病灶中 HLA I 类抗原和 TAP 可能下调。转移病灶中 HLA I 类抗原和 TAP 下调频率较高,可能与疾病的临床病程有关。