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