MMP-9和层粘连蛋白受体在乳腺癌组织中的表达及其与转移和预后的关系

Expression of Matrix Metalloproteinase 9 (MMP-9) and Laminin-Receptor in Breast Carcinoma and Their Correlation with Tumor Metastasis and Prognosis

背景与目的:以往对乳腺癌细胞外基质与肿瘤转移及患者预后之间关系的研究尚少,且结论不一。本研究探讨乳腺癌组织中基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)及层粘连蛋白受体(lamininreceptor,LM-R)表达与肿瘤转移及患者预后的关系。方法:应用免疫组化方法检测80例乳腺癌组织及10例乳腺增生病组织中MMP-9、LM-R的表达,并用计算机图像分析系统测定表达的吸光度值。采用t检验、方差分析及相关分析方法分析它们与肿瘤转移和患者预后的关系。结果:乳腺癌组织中MMP-9表达显著高于乳腺增生病(t=8.87,P<0.05);在乳腺增生病组织中,LM-R表达于基底膜及部分腺泡和导管的腔缘,在乳腺癌组织中表达于细胞质及胞膜;17例癌间质血管基底膜有LM-R表达的癌组织中,LM-R表达高于血管基底膜无LM-R表达组(t=2.02,P<0.05);LM-R表达与组织学分级有关,分化低者,表达水平高(F=3.27,P<0.05);MMP-9及LM-R表达均与淋巴结转移有关,它们在有3个以上淋巴结转移组的表达低于3个以下及无转移组(tMMP-9=3.42,tLM-R=4.31,P<0.05),原发灶与转移灶的表达呈正相关(rMMP-9=0.654,rLM-R=0.755,P<0.001);MMP-9与孕激素受体负相关性(r=-0.363,P<0.05);MMP-9与LM-R之间呈正相关(r=0.503,P<0.01)。

BACKGROUND &OBJECTIVE: Previous researches of breast cancer mainly focused on its parenchyma and prognosis; however, the relationship between extracellular matrix of breast carcinoma and metastasis as well as prognosis was still unknown. The present study was designed to investigate the expression of matrix metalloproteinase 9 (MMP 9) and laminin receptor (LM R) in breast carcinoma and their correlation with tumor metastasis and prognosis. METHODS: The immunohistochemical method was applied to examine the expression of MMP 9 and LM R in 80 samples of breast carcinoma and 10 breast tissues of hyperplasia. The absorbance(A) values that indicate the expression levels were analyzed by computer image technique. t test, chi square test and other related tests were used to analyze their relationship with tumor metastasis and prognosis. RESULTS: The expression of MMP 9 in breast carcinoma was apparently higher than that in hyperplasia (t=8.87, P< 0.05). LM R expressed at the basal membrane and the edge of some acini and ducts in hyperplasia tissues, while expressed at cytoplasm and cellular membrane in breast carcinoma tissues. LM R expression of tumor in 17 cases with LM R expression in basal membrane was higher than that in those without LM R expression in basal membrane (t=2.02, P< 0.05). LM R expression was related to histological grade; the lower the degree of differentiation, the higher the expression level (F=3.27, P< 0.05). The expression of MMP 9 and LM R related to lymphatic metastasis. The expression levels of MMP 9 and LM R in the group which had more than 3 involved lymph node were lower than those in the group which had less than involved 3 lymph node and no involved lymph node (tMMP 9=3.42, tLM R=4.31, P< 0.05). The expression of MMP 9 and LM R in original focus had significantly positive relation to metastasis(rMMP 9=0.654, rLM R=0.755,P< 0.001). MMP 9 had negative relation to progestogen receptor (PR) (r=-0.363,P< 0.05) and positive relation to LM R (r=0.503,P< 0.01). The expression levels of MMP 9 and LM R of the group which survived more than 3 years were lower than that in the group which survived less than 3 years (tMMP 9=3.57, tLM R=4.22, P< 0.05). Both of MMP 9 and LM R were negatively related to the survival of the patients with breast carcinoma (rMMP 9=-0.387, rLM R=-0.369,P< 0.05). CONCLUSION: MMP 9 and LM R are useful indexes for predicting the metastasis and prognosis of breast cancer.