叉头框转录因子M1、Slug、E-cadherin及vimentin在基底细胞样乳腺癌中的表达及其临床意义

Expression of forkhead box M1,Slug,E-cadherein and vimentin in basal-like breast carcinoma and their clinical significance

目的探讨叉头框转录因子M1(FOXM1)、Slug及上皮间质转化的相关蛋白E-钙黏蛋白(E-cadherin)、波形蛋白(vimentin)在基底细胞样乳腺癌(BLBC)、非基底细胞样乳腺癌(non-BLBC)及癌旁乳腺组织中的表达及其临床意义。方法采用免疫组织化学Max Vision法对2005年1月至2014年5月在本院治疗的95例BLBC及其癌旁乳腺组织和100例non-BLBC中FOXM1、Slug、E-cadherin及vimentin的表达进行检测。计数资料的分析运用χ2检验,相关性分析采用Spearman相关性分析。结果在95例BLBC中,FOXM1、Slug和vimentin蛋白的阳性表达率分别为76.84%(73/95)、67.36%(64/95)及52.63%(50/95),显著高于其在non-BLBC[57.00%(57/100)、47.00%(47/100)、31.00%(31/100)]及癌旁乳腺组织[25.26%(24/95)、26.31%(25/95)、9.47%(9/95)]中的表达(χ2=51.673、32.146、41.337,P均=0.000)。BLBC中E-cadherin的阳性表达率为27.37%(26/95),显著低于其在non-BLBC[51.00%(51/100)]及癌旁乳腺组织[75.79%(72/95)]中的表达(χ2=44.590,P=0.000)。FOXM1、Slug、E-cadherin及vimentin的表达均与BLBC的淋巴结转移及临床分期有关,差异具有统计学意义(χ2=4.348、4.669、18.387、21.287,P均<0.050;χ2=7.752、5.366、4.230、7.167,P均<0.050)。BLBC中,FOXM1、Slug与vimentin的表达呈正相关(r=0.279,P=0.006;r=0.284,P=0.005),与Ecadherin表达呈负相关(r=-0.503,P=0.000;r=-0.378,P=0.000),FOXM1与Slug的表达呈正相关(r=0.310,P=0.002)。E-cadherin与vimentin的表达呈负相关(r=-0.363,P=0.000)。结论FOXM1及Slug通过抑制E-cadherin表达、促进vimentin表达从而促进了BLBC的局部侵袭和远处转移,可以作为BLBC预后评价的指标。

Objective To detect the expression and clinical significance of forkhead box M1 （FOXM1）, Slug, E-cadherin and vimentin （the last two were epithelial-mesenehymal transition associated proteins） in basal-like breast cancer （BLBC）. Methods The expressions of FOXM1, Slug, E-eadherin and vimentin were analyzed in 95 cases of BLBC, 95 cases of adjacent breast tissue and 100 cases of non-BLBC treated in our hospital from January 2005 to May 2014 by immunohistochemistry. The enumeration data were analyzed by χ^2 test. The Spearman correlation analysis was performed. Results The positive expression rate of FOXM1, Slug and vimentin in BLBC was 76. 84% （73/95） , 67.36% （64/95） and 52. 63% （50/95） respectively, which was significantly higher than that in non-BLBC [ 57.00% （57/100） ,47.00% （47/11）0）, 31.00% （31/100） ] or adjacent breast tissue [25.26% （24/95） ,26. 31% （25/95） ,9. 47% （9/95） ] （ χ^2 = 51. 673, 32. 146, 41. 337 ,all P= 0. 000）. The positive rate of E-eadherin in BLBC was 27. 37% （26/95）, much lower than that in non-BLBC [ 51.00% （51/100）] and adjacent breast tissue [75.79% （72/95）] （ χ^2 =44. 590, P = 0. 000）. The expressions of FOXM1, Slug, E-cadherin and vimentin were correlated with lymph metastasis and pTNM staging in BLBC patients （χ^2 =4. 348, 4. 669, 18. 387, 21. 287,P〈0. 050; χ^2 = 7.752, 5. 366, 4. 230, 7. 167, P 〈 0. 050）. In BLBC patients, the expression of FOXM1 and Slug had a positive correlation with that of vlmentin （ r = 0. 279, P = 0. 006 ; r = 0. 284, P = 0. 005 ） and had a negative correlation with that of E-cadherin （ r = -0. 503, P = 0. 000 ; r = -0. 378, P = 0. 000 ）. There was a positive correlation between FOXM1 and Slug （r=0. 310, P=0.002） and a negative correlation between E-cadherin and vimentin （r =-0. 363, P = 0. 000）. Conclusion FOXMI and Slug may play an important role in the invasion and metastasis of BLBC by downregulation of E-cadherin and upregulation of vimentin synergistically, which can be used as prognostic factors of BLBC.