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HLA Class I Antigen Down-Regulation in Primary Ovary Carcinoma Lesions: Association with Disease Stage

¹ Department of Anatomy, Pharmacology and Forensic Medicine, University of Parma; ² Institute Trapianti d'Organo e Immunocitologia-Consiglio Nazionale delle Ricerche, Unit of Bologna; ³ Department of Obstetrics and Gynaecology, University of Bologna, Bologna, Italy; Departments of ⁴ Biomedical Sciences and Biotechnologies and ⁵ Experimental and Applied Medicine, University of Brescia, Brescia, Italy; and ⁶ Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Soldano Ferrone, Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: 845-8534; Fax: 845-7613; E-mail: soldano.ferrone{at}roswellpark.org.

Purpose: To investigate TAP1, TAP2, and HLA class I antigen expression in primary ovarian carcinoma lesions and to assess the clinical significance of defects in the expression of these molecules.

Experimental Design: Fifty-one formalin-fixed, paraffin-embedded primary ovarian carcinoma lesions were stained with affinity-purified rabbit anti-TAP1 and anti-TAP2 antibodies and with anti-HLA class I heavy chain monoclonal antibody (mAb) HC-10 using the immunoperoxidase reaction. The results of immunohistochemical staining were correlated with the histopathologic characteristics of the lesions and with patients' survival.

Results: Ovarian surface epithelium, thecal cells of follicles, and stromal cells were stained by anti-TAP1, anti-TAP2, and anti-HLA class I antigen xenoantibodies with a homogeneous pattern. In contrast, no staining of lutheinic cells by these antibodies was detected. Forty-one and 32 out of 51 primary ovarian carcinoma lesions were stained by anti-TAP1 and anti-TAP2 xenoantibodies and by anti-HLA class I antigen mAb HC-10, respectively. The staining patterns by anti-TAP1 and anti-TAP2 xenoantibodies were completely concordant, but did not correlate with that by anti-HLA class I heavy chain mAb HC-10. TAP1 and TAP2 expression was associated neither with the histopathologic characteristics of the lesions nor with clinical variables. On the other hand, HLA class I antigen down-regulation was associated with disease stage: the odds ratio of stage III for HLA class I antigen negative patients was 7.6 (95% confidence interval, 1.9-30.5; P= 0.007), whereas for TAP negative patients was 5.1 (95% confidence interval, 0.9-28.4; P = 0.07). Follow up was available for 39 out of the 51 patients. Multivariate analysis showed that both grading and staging were associated with a higher risk of death, whereas TAP and HLA class I antigen phenotypes were not.

Conclusions: The lack of association between TAP and HLA class I antigen expression is compatible with the possibility that multiple mechanisms underlie HLA class I antigen down-regulation in primary ovarian carcinoma lesions. The potential role of immunologic events in the clinical course of ovarian carcinoma suggests that the association between HLA class I antigen down-regulation and disease progression may reflect the escape of tumor cells from immune recognition and destruction.

Key Words: TAP • HLA antigens • immunohistochemistry • ovarian carcinoma

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