乳腺癌B7-H4的表达与FOXP3+Treg细胞浸润及淋巴结转移的相关性研究

Correlation between B7-H4 expression and tumor-infiltrating FOXP3+Tregs and lymphonode metastasis of human breast cancer

摘要:

目的：研究B7同源体4（B7 homolog 4，B7-H4）在人乳腺癌组织的表达及其与肿瘤内FOXP3+调节性T细胞（Treg）浸润数量和淋巴结转移的相关性。方法：应用SP免疫组织化学法检测B7-H4蛋白在16例正常乳腺组织和79例乳腺癌组织的表达；间接免疫荧光双标染色法观察64例浸润性乳腺癌组织中CD3+ T细胞和FOXP3+ Treg的浸润情况；统计学分析B7-H4的表达与癌间质浸润的FOXP3+ Treg数量和淋巴结转移的相关性。结果：B7-H4在正常乳腺组织、导管内癌和浸润性乳腺癌的阳性表达率分别为6.3%、40.0%和78.1%，其在浸润性乳腺癌中的表达明显高于正常乳腺组织和导管内癌组（P=0.000，P=0.009），但在正常乳腺组织和导管内癌间未见明显差异（P=0.037）；B7-H4的表达与乳腺癌间质浸润的FOXP3+ Treg数量正相关（P=0.368，P=0.003），而与浸润的CD3+ T细胞数量负相关（rs=-0.316，P=0.011）；但B7-H4的表达与乳腺癌的淋巴结转移无关（P >0.05）。结论：B7-H4在乳腺癌异常高表达且与肿瘤局部免疫抑制有关，但与淋巴结转移无明显相关性。

Abstract:

Objective：To investigate the expression of B7 homolog 4（B7-H4） in human breast cancer and to analyze its relationship with number of tumor-infiltrating FOXP3+ Tregs and cancer lymphonode metastasis. Methods：B7-H4 expression was detected by im－munohistochemistry in 16 cases of normal breast tissues and 79 cases of breast cancer. Number of tumor-infiltrating CD3+ T cells and FOXP3+ Tregs was determined by indirect immunofluorescent double-staining in 64 cases of invasive breast cancer. Correlation be－tween B7-H4 expression and number of tumor-infiltrating CD3+ T cells and FOXP3+ Tregs as well as lymphonode metastasis was analyzed. Results：B7-H4 expressed in 6.3% normal breast tissues，40.0% ductal cancer in situ and 78.1% invasive breast cancer. B7-H4 expression in invasive breast cancer was significantly higher than that in normal breast tissues and ductal cancer in situ（P=0.000，P=0.009） without significantly difference between normal breast tissues and ductal cancer in situ（P=0.037）. Intensity of B7-H4 was positively correlated with number of infiltrating FOXP3+ Tregs（rs=0.368，P=0.003） but was negatively correlated with number of infiltrating CD3+ T cells（rs=-0.316，P=0.011） and had no relationship with lymphonode metastasis of breast cancer（P >0.05）. Conclu－sions：B7-H4 overly expresses in breast cancer. B7-H4 is in association with the local antitumor immune inhibition not lymphonode metastasis of tumors.