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Molecular Oncology, Markers, Clinical Correlates |
Departments of Gynecologic Oncology [M. E. G., R. P., M. A. N., R. S. F.], Anatomic Pathology [H-Z. Z.], Biomathematics [L. B. L., E. N. A.], and Pathology [R. L. K.], and The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 [C. D. P.]
Transforming growth factor ß (TGF-ß) is an important family of cytokines that may promote tumor growth in vivo through several mechanisms including interference with antitumor T-cell immune responses, alteration of factors in the stroma and matrix, and the promotion of angiogenesis. TGF-ß isotypes have been detected in malignant and normal ovarian tissues. We have determined by quantitative immunohistochemistry the density of TGF-ß1, TGF-ß2, and human leukocyte antigen (HLA) Class I and Class II antigens on malignant cells in paired primary and metastatic specimens from 10 patients with ovarian carcinoma. Cryostat sections of specimens from the carcinomas and from normal ovaries of three women of similar age without ovarian cancer were stained respectively with specific antibodies to TGF-ß1, TGF-ß2, and HLA Class I and II antigens, and with isotype-matched control antibodies. Antigen density was quantitated blindly as mean absorbance on a SAMBA 4000 image analyzer. TGF-ß1 and TGF-ß2 were overexpressed in both primary and metastatic tumor specimens in comparison with normal ovarian tissue. No statistical correlation was found between the expression of TGF-ß1 or TGF-ß2 and HLA class I or HLA class II, which suggests that TGF-ß isotypes could have effects on the immune system other than down-modulation of these HLA molecules. Furthermore, the lack of association between levels of TGF-ß expression and the reduced expression of HLA molecules could suggest that tumor cells expressing both HLA and TGF-ß may be suitable targets for adaptive immunotherapy. Additional studies are necessary to determine whether TGF-ß expressed by ovarian cancer cells merits evaluation as a therapeutic target.
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