RECK、MMP-9在三阴性乳腺癌组织芯片中的表达及临床意义
|
摘要
目的探讨基质金属蛋白酶抑制剂(RECK)、基质金属蛋白酶-9(MMP-9)在三阴性乳腺癌(TNBC)组织、癌旁组织中的表达及与TNBC临床病理的关系。方法选择绵阳市中心医院乳腺外科2011年5月～2013年7月经病理证实为TNBC的72例石蜡标本及同-患者癌旁组织,利用免疫组化组织芯片技术检测其RECK、MMP-9蛋白的表达。结果 RECK在TNBC组织及癌旁组织中阳性表达率分别为43.06%、80.56%(P=0.000)。TNBC中RECK的表达与临床分期(P=0.009)、组织学分级(P=0.010)、腋窝淋巴结转移情况(P=0.000)相关。MMP-9在TNBC组织及癌旁组织中阳性表达率分别为62.5%、15.28%(P=0.000)。TNBC中MMP-9的表达与肿瘤大小(P=0.017)、临床分期(P=0.001)、组织学分级(P=0.001)、腋窝淋巴结转移状况(P=0.001)、Ki-67表达情况(P=0.034)相关。TNBC中RECK与MMP-9表达呈负相关(r=-0.195,P<0.05)。结论 RECK的表达缺失与MMP-9过度表达与TNBC浸润、转移有关,有望成为TNBC的预后指标,并且有可能成为TNBC治疗的靶点。
Objective To investigate the expression of matrix metalloproteinase inhibitor(RECK), matrix metalloproteinase-9(MMP-9) in triple negative breast cancer(TNBC) and adjacent tissues of TNBC and its relationship with the clinicopathology of TNBC.Methods Immunohistochemical tissue microarray technique was used to detect the expression of RECK and MMP-9 in 72 cases of TNBC and 72 cases of adjacent tissues.Results The positive expression rates of RECK in TNBC and paracancerous tissues were 43.06% and 80.56%(P=0.000). The expression of RECK in TNBC was correlated with clinical stage(P=0.009), histological grade(P=0. 010) and axillary lymph node metastasis(P=0. 000). The positive expression rates of MMP-9 in TNBC and paracancerous tissues were 62.5% and 15.28%(P=0.000). The expression of MMP-9 in TNBC was correlated with tumor size(P=0.017), clinical stage(P=0.001), histological grade(P=0.001) and axillary lymph node metastasis(P=0.034). Negative correlation between RECK and MMP-9 expression in TNBC(r=-0.195,P<0.05).Conclusion The lack of expression of RECK and overexpression of MMP-9 are important biological indicators in the invasion and metastasis of TNBC, which may be the target of TNBC treatment.
Objective To investigate the expression of matrix metalloproteinase inhibitor(RECK), matrix metalloproteinase-9(MMP-9) in triple negative breast cancer(TNBC) and adjacent tissues of TNBC and its relationship with the clinicopathology of TNBC.Methods Immunohistochemical tissue microarray technique was used to detect the expression of RECK and MMP-9 in 72 cases of TNBC and 72 cases of adjacent tissues.Results The positive expression rates of RECK in TNBC and paracancerous tissues were 43.06% and 80.56%(P=0.000). The expression of RECK in TNBC was correlated with clinical stage(P=0.009), histological grade(P=0. 010) and axillary lymph node metastasis(P=0. 000). The positive expression rates of MMP-9 in TNBC and paracancerous tissues were 62.5% and 15.28%(P=0.000). The expression of MMP-9 in TNBC was correlated with tumor size(P=0.017), clinical stage(P=0.001), histological grade(P=0.001) and axillary lymph node metastasis(P=0.034). Negative correlation between RECK and MMP-9 expression in TNBC(r=-0.195,P<0.05).Conclusion The lack of expression of RECK and overexpression of MMP-9 are important biological indicators in the invasion and metastasis of TNBC, which may be the target of TNBC treatment.
引文
[1] Jodele S,Blavier L,Yoon JM,et al. Modifying soil to afect the seed role of stromal derived matrixmetallopro-teinases in cancer progression[J].Cancer Metastasis Rev,2006,25(1):35-43.
[2] Takagi S,Simizu S,Osada H.Reck negatively regulates matrixmetallproteinase-9 transcription[J].Cancer Res,2009,69(4):1502-1508.
[3] Rita CS Figueira,Luciana R Gomes,Joo S Neto,et al. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential[J].BMC Cancer,2009,9(1):20-20.
[4] Vajpeyi R.WHO classification of tumors:Tumours of the Breast and Female Genital Organs[J].Journal of Clinical Pathology,2005,76(1):139-141.
[5] Tavassoli FA,Devilee P.The WHO classification of tumous.Pathology genetics,tumours of breast and female genital organs[J].Lyon:IARC Press, 2003,10(1):32-34,36-37.
[6] 曹旭晨,陈策实,陈佳艺,等.中国抗癌协会乳腺癌诊治指南与规范(2017年版)[J].中国癌症杂志,2017,27(9):719.
[7] Khosravi-Shahi P,Cabezón-Gutiérrez L,Custodio-Cabello S.Metastatic triple negative breast cancer: Optimizing treatment options,new and emerging targeted therapies[J].Asia Pac J Clin Oncol,2018,14(1):32-39.
[8] Hynes RO.The extracellular matrix:not just pretty fibrils[J].Science,2009,326(5957):1216-1219.
[9] Sangaletti S,Chiodoni C,Tripodo C,et al.The good and bad of targeting cancer-associated extracellular matrix[J].Curr Opin Pharmacol,2017,8(35):75-82.
[10] hristine Mehner,Alexandra Hockla,Erin Miller,et al.Tumor cell-produced matrix metalloprot-einase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer[J].Oncotarget,2014,5(9): 2736-2749.
[11] 刘桃桃,申梦琴,王丹丹,等.三阴性乳腺癌中MMP-9及E-cadherin表达的意义[J].实用肿瘤学杂志,2014,28(1):19-23.
[12] Kemmerling R,Weyland D,Kiesslich T,et a1.Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors[J].0ncol Lett,2014,7(3):745-749.
[13] oyal S,Singh UR,Sharma S,et a1.Correlation of mitotic indices,AgNor count,Ki-67 and Bcl-2 with grade and stage in papillary urothelial bladder cancer[J].Urol J,2014,11(1):1238-1247.
[14] 李培栋,王新军,周少龙等.HMGA2、Ki-67和MMP-9在恶性星形细胞瘤中的表达及其相关性[J].使用医学杂志,2015,31(3):404-407.
[15] Noda M, Takahashi C, Matsuzaki T,et al.What we learn from transformation suppressor genes: lessons from RECK.Future Oncol,2010,6(7):1105-1116.
[16] Shen J, Wang B, Zhang T, et al. Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK[J].Cell Physiol Biochem,2018,45(5):1807-1817.
[17] Gomes LR, Fujita A, Mott JD,et al.RECK is not an independent prognostic marker for breast cancer[J].BMC Cancer,2015,15(1):1-11.
[18] 沈波,陈嘉,郑马庆,等.HER-2/neu与RECK mRNA在乳腺癌组织的表达及其意义[J].中华实验和临床病毒学杂志.2012,8(26):279-281.
[19] Zhong Y,Lu YT,Sun Y,et al.Recent opportunities in matrix metalloproteinase inhibitor drug design for cancer[J].Expert Opin Drug Discov,2018,13 (1): 75-87.
[20] Amar S,Fields GB.Potential clinical implications of recent matrix metalloproteinase inhibitor design strategies[J].Expert Rev Proteomics,2015,12 (5): 445-447.
[2] Takagi S,Simizu S,Osada H.Reck negatively regulates matrixmetallproteinase-9 transcription[J].Cancer Res,2009,69(4):1502-1508.
[3] Rita CS Figueira,Luciana R Gomes,Joo S Neto,et al. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential[J].BMC Cancer,2009,9(1):20-20.
[4] Vajpeyi R.WHO classification of tumors:Tumours of the Breast and Female Genital Organs[J].Journal of Clinical Pathology,2005,76(1):139-141.
[5] Tavassoli FA,Devilee P.The WHO classification of tumous.Pathology genetics,tumours of breast and female genital organs[J].Lyon:IARC Press, 2003,10(1):32-34,36-37.
[6] 曹旭晨,陈策实,陈佳艺,等.中国抗癌协会乳腺癌诊治指南与规范(2017年版)[J].中国癌症杂志,2017,27(9):719.
[7] Khosravi-Shahi P,Cabezón-Gutiérrez L,Custodio-Cabello S.Metastatic triple negative breast cancer: Optimizing treatment options,new and emerging targeted therapies[J].Asia Pac J Clin Oncol,2018,14(1):32-39.
[8] Hynes RO.The extracellular matrix:not just pretty fibrils[J].Science,2009,326(5957):1216-1219.
[9] Sangaletti S,Chiodoni C,Tripodo C,et al.The good and bad of targeting cancer-associated extracellular matrix[J].Curr Opin Pharmacol,2017,8(35):75-82.
[10] hristine Mehner,Alexandra Hockla,Erin Miller,et al.Tumor cell-produced matrix metalloprot-einase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer[J].Oncotarget,2014,5(9): 2736-2749.
[11] 刘桃桃,申梦琴,王丹丹,等.三阴性乳腺癌中MMP-9及E-cadherin表达的意义[J].实用肿瘤学杂志,2014,28(1):19-23.
[12] Kemmerling R,Weyland D,Kiesslich T,et a1.Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors[J].0ncol Lett,2014,7(3):745-749.
[13] oyal S,Singh UR,Sharma S,et a1.Correlation of mitotic indices,AgNor count,Ki-67 and Bcl-2 with grade and stage in papillary urothelial bladder cancer[J].Urol J,2014,11(1):1238-1247.
[14] 李培栋,王新军,周少龙等.HMGA2、Ki-67和MMP-9在恶性星形细胞瘤中的表达及其相关性[J].使用医学杂志,2015,31(3):404-407.
[15] Noda M, Takahashi C, Matsuzaki T,et al.What we learn from transformation suppressor genes: lessons from RECK.Future Oncol,2010,6(7):1105-1116.
[16] Shen J, Wang B, Zhang T, et al. Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK[J].Cell Physiol Biochem,2018,45(5):1807-1817.
[17] Gomes LR, Fujita A, Mott JD,et al.RECK is not an independent prognostic marker for breast cancer[J].BMC Cancer,2015,15(1):1-11.
[18] 沈波,陈嘉,郑马庆,等.HER-2/neu与RECK mRNA在乳腺癌组织的表达及其意义[J].中华实验和临床病毒学杂志.2012,8(26):279-281.
[19] Zhong Y,Lu YT,Sun Y,et al.Recent opportunities in matrix metalloproteinase inhibitor drug design for cancer[J].Expert Opin Drug Discov,2018,13 (1): 75-87.
[20] Amar S,Fields GB.Potential clinical implications of recent matrix metalloproteinase inhibitor design strategies[J].Expert Rev Proteomics,2015,12 (5): 445-447.