乳腺癌发生与演进过程中血管生成作用的评价

目的 探讨人乳腺癌前病变、原位癌及浸润性癌中CD34、血管内皮生长因子(VEGF)及其受体Flk-1/KDR的表达变化及血管生成异常与乳腺癌发生发展的关系.方法 应用免疫组织化学技术检测30例正常乳腺、30例普通性增生、30例非典型增生(AH)、20例导管内癌、50例浸润性导管癌组织中微血管密度(MVD)、VEGF及Flk-1/KDR的表达.结果 各组CD34、VEGF及Flk-1/KDR的表达程度不同,浸润性导管癌组最高.随病程演进MVD逐渐增加(P<0.05),VEGF及其受体Flk.1/KDR在血管内皮细胞表达渐进性增高(P<0.05),但在病程初期各主要指标改变不明显,显著变化始于AH阶段.MVD在AH与导管内癌组间差异无统计学意义(P>0.05),VEGF及Flk-1/KDR的表达在AH与导管内癌组间差异有统计学意义(P<0.05).结论 血管生成异常可能是乳腺癌发生过程中的早期事件.VEGF及Flk-1/KDR的表达异常可能是乳腺普通性增生-AH-乳腺癌这一癌性转化过程中血管生成异常的主要始动因素,其可能成为乳腺癌早期诊治的靶标.

Evaluation of angiogenesis in the tumorigenesis and progression of breast cancer

Objectives To investigate the expression of CD34, vascular endothelial growth factor(VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression. Methods One hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were detremined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34. Results The expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR( P<0.05 ), but not in the MVD ( P>0.05 ). Conclusions Abnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.