HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker

• Published in: Cancer research (Chicago, Ill.) Ill.), 2006-09, Vol.66 (18), p.9281-9289
• Main Authors: OGINO, Takeshi, SHIGYO, Hiroshi, ISHII, Hideyuki, KATAYAMA, Akihiro, MIYOKAWA, Naoyuki, HARABUCHI, Yasuaki, FERRONE, Soldano
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - immunology; Antibody Specificity; Antigen Presentation - immunology; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; CD8-Positive T-Lymphocytes - immunology; Cysteine Endopeptidases - biosynthesis; Down-Regulation; Female; HLA-A Antigens - biosynthesis; HLA-A Antigens - immunology; Humans; Laryngeal Neoplasms - immunology; Laryngeal Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Prognosis; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-06-0488

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.