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Clinical Cancer Research Vol. 9, 4043-4051, September 15, 2003
© 2003 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Association of Tapasin and HLA Class I Antigen Down-Regulation in Primary Maxillary Sinus Squamous Cell Carcinoma Lesions with Reduced Survival of Patients1

Takeshi Ogino2, Nobuyuki Bandoh, Tatsuya Hayashi, Naoyuki Miyokawa, Yasuaki Harabuchi and Soldano Ferrone

Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Hokkaido 078-8510 Japan [T. O., N. B., T. H., Y. H.]; Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263 [T. O., S. F.]; and Surgical Pathology Section, Asahikawa Medical College Hospital, Asahikawa 078-8510, Japan [N. M.]

ABSTRACT

Purpose: The purpose of this research was to assess the frequency and clinical significance of antigen processing machinery component and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma (SCC) lesions.

Experimental Design: Formalin-fixed, paraffin-embedded tumor biopsy specimens at pretreatment status from 70 Japanese patients with maxillary sinus SCC were examined for HLA class I antigen and endoplasmic reticulum chaperone molecule expression using an immunohistochemical method. Furthermore, the results of immunohistochemical staining of the lesions were correlated with their histopathological characteristics and with the clinical course of the disease.

Results: Calnexin, ERp57, calreticulin, tapasin, and HLA class I antigens were down-regulated in 13, 13, 24, 69, and 78% of the 70 lesions tested, respectively. Both tapasin and HLA class I antigen expression were significantly correlated with the number of infiltrating CD3+ T cells into tumor lesions (P < 0.01); furthermore, tapasin expression was significantly correlated with tumor differentiation (P = 0.024). Tapasin expression was correlated with that of HLA class I antigens (P < 0.01). Furthermore, tapasin and HLA class I antigen down-regulation in SCC lesions was significantly associated with reduced survival of patients (P = 0.01 and P = 0.002, respectively). Multivariate Cox proportional hazards model analysis identified HLA class I antigen down-regulation as an independent prognostic marker.

Conclusions: Tapasin expression appears to be associated with HLA class I antigen expression in primary maxillary sinus SCC lesions. Furthermore, defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the disease, because these defects were associated with poor prognosis.




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Cancer Research Clinical Cancer Research
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