Tumor necrosis factor-α mRNA and protein in endometrial tumors: Analysis by in situ hybridization and immunocytochemistry

Abstract

Abnormal expression of polypeptide growth factors and their receptors is closely associated with tumorigenic transformation. In this study tumor necrosis factor-α (TNF-α) 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 immunocytochemistry. All samples contained products of the TNF-α gene. Histochemical scores (HS), which reflect the proportion of cells positive for TNF-α message or protein and the intensities of the signals, were higher for epithelial than for stromal cells. Benign lesions (endometrial polyps) contained little TNF-α mRNA or protein, whereas specific message was abundant in proliferative lesions (hyperplasia, adenofibroma). Although neoplastic cells in both low and high grade endometrial tumors contained TNF-α mRNA, two major differences were observed: HS for TNF-α mRNA were significantly less in low grade than in high grade neoplasms, and TNF-α 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 benign and proliferative lesions, TNF-α protein scores in endometrial tumor cells were inversely rather than positively correlated with TNF-α mRNA scores. Collectively, the findings in this study are consistent with the postulate that TNF-α is useful to endometrial tumor cells and suggest that production may increase as cells diverge from normal.