TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA AND PROTEIN IN ENDOMETRIAL TUMORS - ANALYSIS BY IN-SITU HYBRIDIZATION AND IMMUNOCYTOCHEMISTRY

Abnormal expression of polypeptide growth factors and their receptors is closely associated with tumorigenic transformation. In this study t umor necrosis factor-alpha. (TNF-alpha) mRNA and protein were analyzed in polyps and proliferative lesions of endometrium as well as in low and high grade endometrial tumors by using in situ hybridization and i mmunocytochemistry. All samples contained products of the TNF-alpha ge ne. Histochemical scores (HS), which reflect the proportion of cells p ositive for TNF-alpha message or protein and the intensities of the si gnals, were higher for epithelial than for stromal cells. Benign lesio ns (endometrial polyps) contained little TNF-alpha mRNA or protein, wh ereas specific message was abundant in proliferative lesions (hyperpla sia, adenofibroma). Although neoplastic cells in both low and high gra de endometrial tumors contained TNF-alpha mRNA, two major differences were observed: HS for TNF-alpha mRNA were significantly less in low gr ade than in high grade neoplasms, and TNF-alpha message was restricted to the nucleus in low grade adenocarcinoma cells but was abundant in the cytoplasm of high grade tumor cells. In contrast to cells in benig n and proliferative lesions, TNF-alpha protein scores in endometrial t umor cells were inversely rather than positively correlated with TNF-a lpha mRNA scores. Collectively, the findings in this study are consist ent with the postulate that TNF-alpha is useful to endometrial tumor c ells and suggest that production may increase as cells diverge from no rmal. Copyright (C) 1994 by W.B. Saunders Company