【摘要】 目的 Notch信号通路在乳腺癌中存在异常表达,但在不同分子分型乳腺癌中的表达情况鲜见报道。本研究将探讨不同分子分型乳腺浸润性导管癌组织中Notch1和JAG1蛋白表达及其与临床病理特征之间的关系。方法收集滨州医学院附属医院病理科2012-01-06-2014-12-30存档的乳腺浸润性导管癌病例240例,根据ER、PR、HER2、Ki-67免疫组化结果分为管腔A型、管腔B型、HER2过表达型及三阴性型4组,每组60例,采用免疫组化En-Vision法检测不同分子分型乳腺癌中Notch1、JAG1蛋白的表达情况,对各分型乳腺癌组织的阳性表达率进行统计学分析。结果各分型乳腺癌组织中Notch1的阳性表达差异有统计学意义(P=0.010,P<0.05),其中三阴性乳腺癌(86.67%)与管腔A型(56.67%)比较(P<0.001),HER2过表达型(83.33%)与管腔A型(56.67%)比较,差异均有统计学意义,P<0.001;Notch1的阳性表达与淋巴结转移相关(P=0.017,P<0.05),与临床分期(P=0.005,P<0.01)、组织学分级(P=0.009,P<0.01)显著相关,与ER表达(r_s=-0.206,P=0.001,P<0.01)、PR表达(r_s=-0.187,P=0.005,P<0.01)显著负相关,而与患者年龄、肿块大小无关。各分型乳腺癌组织中JAG1的阳性表达差异有统计学意义(P=0.035,P<0.05),以三阴性乳腺癌阳性表达率最高,但各组间两两比较差异无统计学意义;JAG1阳性表达与ER表达(r_s=-0.142,P=0.015,P<0.05)、PR表达(r_s=-0.127,P=0.035,P<0.05)呈负相关;Notch1和JAG1之间无明显相关性。结论 Notch1阳性表达与ER、PR表达显著负相关,与乳腺癌的组织学分级、淋巴结转移及临床分期密切相关,并在HER2过表达型,尤其是三阴性乳腺癌组织中存在高表达,有可能成为三阴性乳腺癌新的治疗靶点。更多还原

【Abstract】 OBJECTIVE There was high expression of Notch signaling pathway in breast carcinoma,which was rarely reported in different molecular subtypes of breast carcinoma.The study aimed to investigate the expressions and clinicopathological significances of Notch1 and JAG1proteins in different molecular subtypes of breast invasive ductal carcinomas.METHODS Immunohistochemical method was employed to detect the expressions of Notch1 and JAG1 in 240 cases of breast invasive ductal carcinomas which were obtained between the period 2012-01-06 and 2014-12-30 in Binzhou Medical Univer_sity Hospital and classified into luminal A,luminal B,HER2 positive and triple-negative breast carcinoma(TNBC)by ER,PR,HER2 and Ki-67.RESULTS There were significant differences in the expressions of Notch1 in different molecular subtypes of breast carcinoma(P=0.010)respectively between TNBC(86.67%)and luminal A(56.67%)breast carcinoma(P<0.001),HER2 positive(83.33%)and luminal A(56.67%)breast carcinoma(P<0.001).An association was identified between the expression of Notch1 and lymph node metastasis(P=0.017),clinical stages(P=0.005),tumor grade(P=0.009),negative ER(r_s=-0.206,P=0.001)and PR(r_s=-0.187,P=0.005),no association was observed for tumor size or patients’ age.The expression of JAG1 in different molecular subtypes of breast carcinoma showed differences(P=0.035),and TNBC exhibited higher JAG1 expression than the other subtypes,there was no significant difference between each two molecular subtypes of breast carcinoma.The expression of JAG1 was associated with the negative ER(r_s=-0.142,P=0.015)and PR(r_s=-0.127,P=0.035).There was no correlation between the expression of Notch1 and JAG1 in breast carcinoma.CONCLUSIONS The expression of JAG1 is associated with negative ER and PR.The JAG1 protein is highly expressed in the TNBC,but there is no relationship between Notch1 and JAG1.The expression of Notch1 is not only related with tumor grade,lymph node metastasis and clinical stages but also with negative ER and PR.The Notch1 protein shows high expression in HER2 positive subtypes,especially in TNBC,which may provide a new therapeutic target of TNBC.更多还原