Aberrant Expression of the Von Hippel-Lindau Gene in Human Endometrial Hyperplasia and Endometrial Carcinoma

Abstract

The purpose of this study was to determine whether aberrant expression of the von Hippel-Lindau (VHL) gene in human hyperplastic and malignant endometrial tissues was involved in endometrial carcinogenesis. Fresh tissue samples of endometrial hyperplasia consisting of simple (n = 26), complex (n = 23), and atypical hyperplasia (n = 20); endometrial carcinoma (n = 17); and normal endometrium (n = 40) were measured using Western blotting and real-time reverse transcription polymerase chain reaction. Paraffin-embedded sections of endometrial hyperplasia (n = 90), endometrial carcinoma (n = 30), and normal endometrium (n = 60) were detected by immunohistochemical method. Von Hippel-Lindau staining was present in the cytoplasm of epithelial cells and stroma. A decreased expression of VHL mRNA in endometrial hyperplasia from simple, complex, to atypical hyperplasia was observed. There were statistical differences on VHL messenger RNA (mRNA) levels among simple, complex, and atypical hyperplasia (P < 0.01). The VHL mRNA levels in endometrial carcinoma were significantly lower than those in normal endometrium, simple hyperplasia, or complex hyperplasia (P < 0.01) but similar to those in atypical hyperplasia (P > 0.05). Von Hippel-Lindau protein levels by Western blotting and staining intensity by immunohistochemistry were coincident with the VHL mRNA levels. Aberrant expression of the VHL gene is associated with the risk of endometrial hyperplasia progressing to endometrial carcinoma, and its expression levels are useful as a predictive indicator for endometrial carcinoma.