Background: The etiology and biology of ovarian carcinogenesis is largely unknown. Recent results have indicated prognostic significance of growth factors in this malignancy. TGF-beta is a widely distributed growth factor with multifactorial effects in in vitro systems. Studies on the in vivo expression pattern of TGF-beta and its receptors might help us to understand its biologic significance in this malignancy.
Experimental design: Tissue samples of normal ovary and benign as well as malignant ovarian neoplasms were examined for expression of transforming growth factor (TGF)-beta 1, -beta 2, and -beta 3, the latent TGF-beta-binding protein (LTBP), TGF-beta type I (T beta R-II) receptors and endoglin by immunohistochemistry and in situ hybridization. Furthermore, the results of the immunohistochemical analysis were compared with patient survival.
Results: Expression of all ligands was significantly increased in tumor cells compared with the normal epithelial cells. In contrast, LTBP immunoreactivity was detected significantly more often in normal epithelium than in tumor cells. T beta R-I and T beta R-II as well as endoglin were found in tumor tissues and normal ovary without any difference among the groups. In the blood vessels of malignant tumors, significantly increased TGF-beta 1 reactivity and decreased TGF-beta 2 reactivity were found when they were compared with those of normal ovaries and benign tumors. Patients with malignant tumors expressing TGF-beta 1, T beta R-I, or endoglin in blood vessels demonstrated longer survival than those having negatively stained tumors. In contrast, positive endoglin staining in tumor cells correlated with decreased survival even in advanced disease or in patients having residual tumor bulk after surgery.
Conclusions: The differential expression of TGF-beta ligand and the significant correlations between expression of ligands or receptors and patient survival indicate involvement of the TGF-beta system in ovarian tumor development.