子宫内膜增生过长和子宫内膜样腺癌中VEGF和TSP-1表达与血管新生研究

Angiogenesis and expression of vascular endothelial growth factor and thrombospondin 1 in endometrial hyperplasia and Endometrioid Adenocaranoma

目的 探讨子宫内膜增生过长及子宫内膜样腺癌中血管内皮生长因子(VEGF)和血小板反应素1(TSP-1)表达与血管新生的关系以及对子宫内膜样腺癌的发生、发展中的作用。方法 采用免疫组织化学方法分别检测子宫内膜正常(12例)、增生过长(13例)、不典型增生(18例)及子宫内膜样腺癌(50例)中微血管密度(MVD)、VEGF及TSP-1表达情况。结果 子宫内膜不典型增生和内膜样腺癌中MVD明显大于内膜正常及增生过长者(P<0.05),子宫内膜样腺癌I_A期与不典型增生二者的MVD差异无显著性(P>0.05),而与正常内膜和增生过长者差异有显著性(P<0.05);VEGF表达与上述不同内膜病变中MVD呈正相关(r=0.843,P=0.0001),而TSP-1表达仅在子宫内膜样腺癌中分别与MVD和VEGF呈负相关趋势(r=-0.233,P=0.1041;r=-0.235,P=0.1003);在子宫内膜样腺癌中TSP-1间质高表达且具有异质性。结论 子宫内膜不典型增生和子宫内膜样腺癌中VEGF对血管新生起正向调节作用;TSP-1在部分腺癌患者中表达增强,但其负向调节作用较弱,可能会使血管新生开关平衡失调,与子宫内膜样腺癌发生及发展有关。

Objective To investigate the relationship between angiogenesis and expression of vascular endothelial growth factor (VEGF) and thrombospondin 1 (TSP- 1) in endometrial hyperplasia and endometioid adenocarcinoma, to reveal the role of angiogenesis, VEGF and TSP- 1 in the carcinogenesis and progression of endometrioid adenocarcinoma.Methods Angiogenesis was evaluated by microvessel density (MVD) . MVD, VEGF and TSP- 1 were stained immunohistochemically in normal (12 cases), hyperplastic (13 cases) and atypical hyperplastic endometrium (18 cases), as well as endometrioid adenocarcinoma (50 cases) .Results MVD in the atypical endometrial hyperplasia or the endometrioid adenocarcinoma was significantly higher than those in the normal and the hyperplastic endometrium (P < 0.05) . There was no remarkable difference between MVD in stage IA endometrioid adenocarcinoma and atypical endometrial hyperplasia (P > 0.05), but remarkable difference between MVD in stage IA and endometrial hyperplasia ( P < 0.05) . The expression of VEGF was positively correlated with MVD in different endometrial lesions mentioned (r= 0.843, P = 0.0001); however, there were inverse trends of the expression of TSP- 1 with MVD and VEGF, only in endometrioid adenocarcinoma (r = -0.233, P = 0.1041; r= -0.235, P = 0.1003) . There was hetero-genicity of increased expression of TSP - 1 in stroma of endometrioid adenocarcinoma. Conclusions There is higher activity of angiogenesis in atypical endometrial hyperplasia and endometrioid adenocarcinoma. Moreover, the positive regulation of VEGF may play a key part, while its negative regulation of TSP- 1 exerts less effect on the abnormal increased activity of angiogenesis, which made the balance of angiogenic switch out of control and related to the carcinogenesis and progression of endometrioid adenocarci-