乳腺癌发生过程中ER、PR、HER-2及WT1蛋白表达变化的研究

Changes of ER, PR, HER-2 and WT1 protein expression during the development of breast cancer

目的探讨雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER-2)及Wilms瘤基因1(WT1)在乳腺癌发生过程中的表达变化。方法收集2011年1月至2011年12月95例经活检病理组织学检查确诊的乳腺疾病患者(乳腺导管上皮增生22例、乳腺导管上皮不典型增生23例、导管内癌23例及导管内癌微浸润27例),取组织病理切片后采用免疫组化SP法检测ER、PR、HER-2和WT1蛋白的表达水平,分别观察在导管上皮增生、不典型增生、导管内癌和导管内癌微浸润4种乳腺癌不同分期水平中的表达情况。结果ER、PR在各组中的阳性表达率无明显差异;HER-2在乳腺导管上皮增生、导管上皮不典型增生、导管内癌和导管内癌伴微浸润中的阳性表达率分别为0(0/22)、4.3%(1/23)、34.8%(8/23)和51.9%(14/27),其表达逐渐增加(P<0.001);WT1的阳性表达率分别为31.8%(7/22)、60.9%(14/23)、13.0%(3/23)和22.2%(6/27),在不典型增生患者中最高,差异有统计学意义(P=0.002)。在导管内癌的患者中,ER、PR的表达与否(+/﹣)和WT1阳性率呈一定的相关性,ER或PR阳性表达者其WT1阳性率更高(P<0.05)。结论ER、PR表达的逐渐增加可提示乳腺癌的发生发展,而HER-2在乳腺癌的启动中发挥重要作用,WT1不仅发挥了癌基因的功能,同时也可参与肿瘤的侵袭和转移,促进其演进过程。

Objective To explore the effect and mechanism of estrogen receptor(ER),progesterone(PR),human epidermal growth factor receptor-2(HER-2)and Wilms’tumor gene 1(WT1)in carcinogenesis and development in breast cancer,so as to provide new ways of molecular targeted therapy.Methods Totally 95 patients from Jan 2011 to Dec 2011(22 ductal epithelial hyperplasia,23 ductal epithelial atypical hyperplasia,23 intraductal carcinoma and 27 intraductal infiltrating carcinoma)who were diagnosed definitely as breast diseases with histological examination were included.Expression levels of ER,PR,HER-2 and WT1 were detected using immunohisitochemistry method and analyzed by relative analysis.Results ER and PR expression had no significant difference between both groups.The positive expression rates of HER-2 in ductal epithelial hyperplasia,ductal epithelial atypical hyperplasia,intraductal carcinoma and intraductal infiltrating carcinoma were 0%(0/22),4.3%(1/23),34.8%(8/23)and 51.9%(14/27),with the increasing trend(P<0.001).The positive expression rate of WT-1 in these four groups were 31.8%(7/22),60.9%(14/23),13.0%(3/23)and 22.2%(6/27)with the highest expression in atypical hyperplasia(P=0.002).In the intraductal carcinoma patients,the expression of ER and PR(+/-)were associated with the positive ratio of WT-1(P<0.05).There were higher positive ratios of WT-1 in patients with positive ER or PR.Conclusion The gradually increase of ER and PR positive ratios indicated carcinogenesis and development of breast cancer.HER-2 participated in the initial process of breast cancer.WT-1 acted both as an oncogene and the factor of invasion and migration,which promoted breast cancer evolution.