The expression of hDlg as a biomarker of the outcome in malignant fibrous histiocytomas

Abstract

The human homologue of Drosophila disc large tumor suppressor protein (hDlg) is one of the proteins known to act cooperatively in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. An abnormal expression of hDlg has been reported in several cancer types. However, the expression of hDlg in soft-tissue sarcomas has not yet been reported. We examined the expression of hDlg immunohistochemically in 46 specimens of malignant fibrous histiocytoma (MFH). The expression of hDlg was negative in 19 specimens, weak in 4, moderate in 16, and strong in 7. The patients with a weak or negative expression of hDlg had a significantly shorter metastasis-free survival rate and disease-free survival rate in comparison with those with a strong or moderate expression in both univariate analysis (p=0.0287 and 0.0237, respectively; log-rank test) and multivariate analysis (p=0.0087 and 0.0126, respectively; Cox proportional hazards regression model). Moreover, the patients with a weak or negative expression of hDlg had a significantly shorter overall survival rate in comparison with those with a strong or moderate expression in a univariate analysis (p=0.0214; log-rank test). This is the first report to demonstrate that a reduced expression of hDlg protein is an independent negative prognostic factor for MFH.