Institute of Reproductive Immunology, Jinan University, Guangzhou, China.
Int J Gynecol Cancer. 2011 Apr;21(3):430-4. doi: 10.1097/IGC.0b013e31820c5903.
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.
本研究旨在探讨人子宫内膜增生和恶性组织中von Hippel-Lindau(VHL)基因的异常表达是否与子宫内膜癌变有关。
采用Western blot和实时逆转录聚合酶链反应检测单纯性(n=26)、复杂性(n=23)和非典型性子宫内膜增生(n=20)、子宫内膜癌(n=17)和正常子宫内膜(n=40)的新鲜组织样本。采用免疫组织化学法检测子宫内膜增生(n=90)、子宫内膜癌(n=30)和正常子宫内膜(n=60)石蜡包埋切片。
VHL 染色定位于上皮细胞和基质细胞的细胞质中。从单纯性、复杂性到非典型性子宫内膜增生,VHL mRNA 的表达逐渐降低。单纯性、复杂性和非典型性子宫内膜增生之间的 VHL 信使 RNA(mRNA)水平存在统计学差异(P<0.01)。子宫内膜癌的 VHL mRNA 水平明显低于正常子宫内膜、单纯性增生或复杂性增生(P<0.01),但与非典型性增生相似(P>0.05)。Western blot 检测的 VHL 蛋白水平和免疫组化染色强度与 VHL mRNA 水平一致。
VHL 基因的异常表达与子宫内膜增生进展为子宫内膜癌的风险相关,其表达水平可作为预测子宫内膜癌的指标。