CD147、MMP-9和p-ERK在乳腺癌中的表达及临床意义

Expression and CD147,MMP-9 and p-ERK in invasive ductal carcinoma of breast and its significance

目的研究细胞外基质金属蛋白酶诱导因子CD147、基质金属蛋白酶9(MMP-9)和磷酸化细胞外信号调节激酶(p-ERK)在乳腺癌组织中的表达及意义。方法应用免疫组化EnvisionTM二步法检测96例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)、34例导管内癌(ductal carcinoma in situ,DCIS)及10例乳腺腺病中CD147、MMP-9及p-ERK蛋白的表达,并分析其与临床病理参数的相关性。结果CD147、MMP-9和p-ERK在IDC中阳性表达率分别为59.4%、54.2%和52.1%,而DCIS的表达阳性率则分别为35.3%、32.6%和29.4%,两组差异具有显著性(P<0.05)。乳腺腺病均表达阴性。CD147和MMP-9表达与IDC的肿块大小(r=0.336;0.306,P<0.05)、TNM分期(r=0.384;0.308,P<0.01)、组织学分级(r=0.272;0.323,P<0.05)、淋巴结转移(r=0.276;0.251,P<0.05)和术后5年生存率(r=0.225;0.251,P<0.05)均呈正相关。CD147与MMP-9蛋白的表达与患者年龄无关。p-ERK蛋白则与IDC的组织学分级(r=0.301,P<0.05)相关,与其它指标均无关。Spearman相关分析,显示在乳腺IDC中CD147与MMP-9的表达呈正相关(r=0.261,P<0.05),p-ERK与CD147和MMP-9蛋白的表达均无相关性(r=0.013;0.122,P>0.05)。结论CD147及MMP-9在乳腺IDC中表达显著增高并呈正相关性,在乳腺癌的侵袭及转移过程中可能起重要作用。CD147诱导和刺激MMP-9蛋白表达可能与MAPK途径有关。

Objective To evaluate the expression of extracellular matrix metalloproteinase inducer （CD147）, matrix metalloproteinase 9 （MMP-9） and phosphorylated activated extracelular signal-regulated kinase （p-ERK） proteins in invasive ductal carcinoma （IDC） of breast and its significance. Methods The expression of CD147, MMP-9 and p-ERK was immunohistochemically examined in 96 cases of IDC of breast, 34 cases of ductal carcinoma in situ （DCIS） and 10 cases of breast adenosis. Results The positive rates of CD147,MMP-9 and p-ERK were 59.4% ,54.2% and 52.1% in IDC of breast, which were significantly higher than those in DCIS of breast （35.3% ,32.6% ,29.4%） and breast adenosis （0%）. CD147 and MMP-9 proteins expressions were positively related to tumor size （r - 0. 336; 0. 306, P 〈 0.05）, TNM stage （r= 0. 384; 0. 308,P〈0. 01）,histological grading （r=0. 272;0. 323,P〈0. 05）,lymph node metastasis （r=0. 276;0. 251,P〈0.05） and 5- year survival rate （r=0. 225;0. 251,P〈0.05）,but unrelated to age of patients, p-ERK protein expressions was related only to histological grading （r=0. 301 ,P〈0.05）. CD147 expression was correlated with MMP-9 （r=0. 261 ,P〈0.05） ,but p-ERK expression showed no correlation with expression of both CD147 and MMP-9 （r=0. 013;0. 122,P〉 0. 05）. Conclusions Overexpression of CD147 and MMP-9 may play an important role in the aggression and metastasis of human breast cancer. Tumor-derived CD147 stimulates MMP-9 collagenase transcription may be mediated via MAPK signaling pathways other than ERK.