title: HLA class I antigen and transporter associated with antigen processing downregulation in metastatic lesions of head and neck squamous cell carcinoma as a marker of poor prognosis.
abstract: 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.
authors.affiliation: Head and Neck Cancer Center, Hokuto Hospital, Hokkaido 080-0833, Japan. bando@hokuto7.or.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Bandoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogino
authors.forename: Akihiro
authors.initials: A
authors.lastname: Katayama
authors.forename: Miki
authors.initials: M
authors.lastname: Takahara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Katada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C071692:TAP2 protein, human