乳腺癌组织中LYVE-1和PROX-1的表达及临床意义
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摘要
目的检测淋巴管内皮细胞透明质酸受体1(LYVE-1)和同源盒基因转录因子1(PROX-1)在人乳腺癌组织中的表达,探讨淋巴管密度在肿瘤淋巴结转移中的临床意义。方法收集80例乳腺浸润性导管癌和35例乳腺良性增生组织,采用免疫组织化学SP法检测LYVE-1和PROX-1的表达。结果乳腺癌组织中LYVE-1和PROX-1各自标记的淋巴管密度均明显高于乳腺增生组织,差异均有统计学意义(均P<0.01),且与肿瘤淋巴结转移密切相关,有淋巴结转移者均高于无淋巴结转移者(均P<0.01);PROX-1在癌细胞内的表达,不同的肿瘤病理学分级和临床分期之间差异均有统计学意义(均P<0.01)。结论乳腺浸润性导管癌组织中淋巴管生成增多,淋巴管密度与肿瘤淋巴结转移相关,PROX-1可能与乳腺癌发生、发展及淋巴结转移相关。
Objective To investigate the expressions of LYVE-1and PROX-1in human breast carcinoma and the clinical significance of lymphatic vessel density.Methods Immunohistochemistry(SP method)was used to detect the expressions of LYVE-1and PROX-1in 80 specimens of breast invasive ductal carcinoma and 35 specimens of breast hyperplasia.Results The density of lymphatic vessels positive for LYVE-1or PROX-1was significantly higher in breast carcinoma than in breast hyperplasia(P<0.01).There was a significant correlation between lymphatic vessel density and lymph node metastasis(P<0.01).A negative correlation was noted between the PROX-1expression in carcinoma cells and tumor grade(P<0.01)or TNM stage(P<0.01).Conclusion Lymphangiogenesis is increased in breast carcinoma,which is associated with lymph node metastasis.PROX-1may be involved in tumorigenesis,progression and lymphatic metastasis in breast cancer.
Objective To investigate the expressions of LYVE-1and PROX-1in human breast carcinoma and the clinical significance of lymphatic vessel density.Methods Immunohistochemistry(SP method)was used to detect the expressions of LYVE-1and PROX-1in 80 specimens of breast invasive ductal carcinoma and 35 specimens of breast hyperplasia.Results The density of lymphatic vessels positive for LYVE-1or PROX-1was significantly higher in breast carcinoma than in breast hyperplasia(P<0.01).There was a significant correlation between lymphatic vessel density and lymph node metastasis(P<0.01).A negative correlation was noted between the PROX-1expression in carcinoma cells and tumor grade(P<0.01)or TNM stage(P<0.01).Conclusion Lymphangiogenesis is increased in breast carcinoma,which is associated with lymph node metastasis.PROX-1may be involved in tumorigenesis,progression and lymphatic metastasis in breast cancer.
引文
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[2]Miao H,Hartman M,Bhoo-Pathy N,et al.Predicting survival of de novo metastatic breast cancer in asian women:systematic review and validation study[J].PLoS One,2014,9(4):e93755.
[3]Bernaudin J F,Kambouchner M,Lacave R.Lymphatic vascular system,development and lymph formation[J].Review Rev Pneumol Clin,2013,69(2):93-101.
[4]Miyazaki T,Kato H,Fukuchi M,et al.EphA2overexpression correlations with poor prognosis in esophageal squamous cell carcinoma[J].Int J Cancer,2003,103(5):657-663.
[5]Fujinaga T,Kumamaru W,Sugiura T,et al.Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva[J].Int J Oncol,2014,44(5):1614-1624.
[6]Siveen K S,Sikka S,Surana R,et al.Targeting the STAT3signaling pathway in cancer:Role of synthetic and natural inhibitors[J].Biochim Biophys Acta,2014,1845(2):136-154.
[7]Penault-Llorca F,Mishellany F,Fouilhoux G,et al.Diagnostic approach for breast cancer classification[J].Rev Prat,2013,63(10):1384-1390.
[8]Wigle J T,Oliver G.Prox1function is required for the development of the murine lymphatic system[J].Cell,1999,98(6):769-778.
[9]Hong Y K,Detmar M.Prox1,master regulator of the lymphatic vasculature phenotype[J].Cell Tissue Res,2003,314(1):85-92.
[10]Wang C A,Jedlicka P,Patrick A N,et al.SIX1induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer[J].J Clin Invest,2012,122(5):1895-1906.
[11]Skobe M,Hawighorst T,Jackson D G,et al.Induction of tumor lymphangenesis by VEGF-C promotes breast cancer metastasis[J].Nat Med,2001,7(2):192-198.
[12]Versmold B,Felsberg J,Mikeska T,et al.Epigenetic silencing of the candidate tumor suppressor gene PROX1in sporadic breast cancer[J].Int J Cancer,2007,121(3):547-554.
[13]王鸿雁,范良生,黄浩,等.Wnt2B通过NF-κB/p65调节乳腺癌细胞的凋亡[J].华中科技大学学报:医学版,2012,41(4):409-414,422.
[14]Shimoda M,Takahashi M,Yoshimoto T,et al.A homeobox protein,prox1,is involved in the differentiation,proliferation,and prognosis in hepatocellular carcinoma[J].Clin Cancer Res,2006,12(20Pt 1):6005-6011.