DLL4、COX-2和MMP-2在乳腺癌组织中的表达及临床意义

Expressions of DLL4,COX-2 and MMP-2 in breast cancer tissues and its significance

目的探讨Delta样配体4(DLL4)、环氧合酶-2(COX-2)和基质金属蛋白酶-2(MMP-2)在不同乳腺癌分子亚型组织中的表达情况及意义。方法采用免疫组化SP法检测乳腺癌(Luminal A型41例,Luminal B型18例,HER-2过表达型22例,基底细胞样型19例)组织100例及癌旁组织40例中DLL4、COX-2和MMP-2的表达情况,并分析三者表达及与淋巴结转移的相关性。结果 DLL4、COX-2和MMP-2在乳腺癌组织中的阳性表达率分别为73.0%、81.0%和93.0%,均明显高于癌旁组织(P<0.05)。在不同分子亚型乳腺癌组织中,DLL4、COX-2和MMP-2在HER-2过表达型乳腺癌组织中的阳性表达率分别为95.5%、100.0%和100.0%,在基底细胞样型乳腺癌组织中分别为89.5%、94.7%和100.0%,均高于Luminal A型和Luminal B型乳腺癌组织(P<0.05)。DLL4、COX-2和MMP-2在有淋巴结转移的乳腺癌组织中阳性表达率分别为88.7%、92.5%和96.2%,显著高于无淋巴结转移者的阳性表达率(P<0.05)。DLL4分别与COX-2、MMP-2表达呈正相关(r=0.215,P<0.05;r=0.435,P<0.05)。结论 DLL4、COX-2和MMP-2在基底细胞样型和HER-2过表达型乳腺癌组织中呈高表达,DLL4、COX-2和MMP-2共同参与乳腺癌的发生、发展及浸润转移,联合检测三者表达可评估乳腺癌的转移情况。

Objective To study the expressions of DLIA （ delta-like ligand 4） , COX-2 （ Cyclooxygenase-2 ） and MMP-2 （ ma- trix metalloproteinase-2） in different molecular subtypes of breast cancer and analyze their correlation. Methods The expressions of DLL4, COX-2 and MMP-2 were determined by SP immunohistochemistry in 100 cases of breast carcinoma （41 luminal A, 18 lumianl B, 22 HER-2 over-expression and 19 basal-like subtypes） and 40 cases of adjacent normal breast tissues. Then the correlation of DLL4, COX-2 and MMP-2 expression with lymph node metastasis was analyzed. Results The positive expression rates of DLIA, COX-2 and MMP-2 in breast cancer were 73.0% , 81.0% and 93.0% , significantly higher than those in adjacent normal breast tis- sues（P〈0. 05）. The positive rates of DLL4, COX-2 and MMP-2 were 95.5%, 100. 0% and 100. 0% in HER-2 over-expression type, and 89.5% , 94. 7% and 100. 0% in basal-like subtype. They were significantly higher than those in luminal A and lmninal B subtypes（P 〈 0. 05）. The expression of DLIA, COX-2 and MMP-2 in lymph node metastasis group were 88.7% , 92.5% and 96.2% respectively, higher than those without lymph node metastasis group（ P 〈 0. 05 ）. Positive correlation could be found between DLIA and COX-2, MMP-2 expression（r=0.215, P〈0.05; r=0.435, P〈0.05）. Conclusion DLL4, COX-2 and MMP-2 are highly ex- pressed in HER-2 over-expression and basal-like subtypes of breast cancer. These results suggest that they might be important factors in breast carcinogenesis, development and metastasis. These proteins are indicators of metastasis of breast cancer.