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Tumor Necrosis Factor Expression by Human Ovarian Carcinoma in Vivo¹

Laboratory of Clinical Pharmacology, Dana Farber Cancer Institute, Boston, Massachusetts 02115 [H. T., N. W., K. A., D. K.]; New England Deaconess Hospital, Boston, Massachusetts 02215 [C. O., J. N.]; Department of First Surgery, Jikei University, Tokyo, Japan [K. S.]; and Department of Human Oncology, University of Wisconsin, Madison, Wisconsin 53792 [D. S.]

Tumor necrosis factor (TNF) is a cytokine produced by monocytes and other cells with selective cytolytic activity against some but not all tumor cells. Cellular resistance to the cytolytic effects of TNF has been reported to be associated with autocrine production of TNF by the target cells. The purpose of this study was to determine whether or not human tumors produce tumor necrosis factor in vivo. Ovarian carcinoma tissue from 25 patients with ovarian carcinoma was examined for the presence of TNF. Four of 5 ascites fluid specimens and tissue sections of 16 of 20 patients were positive for TNF by immunoperoxidase staining. The source of the immunoreactive protein was further examined by in situ hybridization studies. TNF mRNA was detectable in each of the ascites specimens and 7 of 16 tissue sections that were positive by immunoperoxidase staining. These findings suggest that TNF is produced by some human tumors in vivo and that the association between TNF production and resistance to TNF antitumor action may be clinically relevant.

¹ This work was supported in part by Department of Health and Human Services Grant RO-CA47722. The authors gratefully acknowledge the financial support of Asahi Chemical Industry for the cost of color reproductions.

² To whom requests for reprints should be addressed, at Department of Human Oncology, K4/414, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792.

Received 3/18/91. Accepted 5/31/91.

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