title: HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker.
abstract: We have investigated the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) lesions and assessed the clinical significance of these defects. To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for APM component and HLA class I antigen expression by immunohistochemistry. Calnexin, calreticulin, and ERp57 were down-regulated in approximately 25% of the lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down-regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was significantly correlated with HLA class I antigen expression suggesting APM component defects as a mechanism underlying HLA class I antigen down-regulation in laryngeal SCC lesions. The expression of most APM components and HLA class I antigens was correlated with the extent of CD8+ T cell infiltration into tumor lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8+ T cell infiltration were significantly associated with reduced patients' survival. Multivariate analysis identified HLA class I antigen down-regulation as an independent unfavorable prognostic marker. This association is likely to reflect the reduction in the extent of CD8+ T cell infiltration in laryngeal SCC lesions.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Division of Surgical Pathology, Asahikawa Medical College Hospital, Asahikawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shigyo
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishii
authors.forename: Akihiro
authors.initials: A
authors.lastname: Katayama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyokawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017951:Antigen Presentation / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D015536:Down-Regulation; D005260:Female; D015234:HLA-A Antigens / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D015234:HLA-A Antigens; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases