三阴性乳腺癌中上皮-间充质转化相关标记分子的研究

Molecular markers of epithelial - to - mesenchymal transition in triple - negative breast cancer

目的检测乳腺癌细胞中上皮．间充质转化（EMT）相关分子标志物如钙黏蛋白、波形蛋白、表皮生长因子受体（EGFR）、血小板源生长因子（PDGF）-D和核因子-KB（NF—KB），讨论它们与EMT之间的关系以及在乳腺癌进展中的作用。方法应用免疫组织化学方法检测57例浸润性导管腺癌患者钙黏蛋白、波形蛋白、EGFR、NF-κB和PDGF-D的表达。患者分为3组：A[雌激素受体（ER）^＋和／或孕激素受体（PR）^＋，人类表皮生长因子受体-2（Her-2）／neu^-]、B（ER^＋和／或PR^＋，Her-2／neu＋）、C（三阴性：ER^-、PR^-、Her-2／neu^-）。免疫组织化学镜下阅片记录染色强度（0、＋、＋＋和＋＋＋）和阳性细胞百分比，并将数据进行统计分析。结果膜钙黏蛋白在所有57例中均表现为阳性（100％），然而，与A组比较，胞质钙黏蛋白在B组和C组有表达（B组：21％，C组：7％，A组：0％）。所有A组病例波形蛋白和EGFR均为阴性。三阴性乳腺癌病例中波形蛋白、EGFR和NF—KB的表达上调，与A组和B组比较差异有统计学意义（P〈0．05）。结论波形蛋白、EGFR和NF—KB在三阴性乳腺癌中表达明显上调，与这-类型肿瘤细胞的高侵袭特性-致。

Objective To investigate the molecular alterations in breast cancer samples using epi- thelial- to- mesenchymal transition （EMT） markers such as E -eadherin, vimentin, epidermal growth factor receptor （EGFR）, platelet -derived growth factor （PDGF） -D, and nuclear factor - KB （NF - KB） to reveal their roles in the EMT and breast cancer progression. Methods In 57 cases of invasive due- tal breast carcinoma, the expression of E - eadherin, vimentin, EGFR, NF - KB, and PDGF - D was de- tected using immunohistochemistry. Tumors were categorized into three groups： A [ estrogen receptor （ER） ^＋ , and/or progesterone receptor （PR） ^＋ , human epidermal growth factor receptor- 2 （Her- 2 ）/ neu ^- ] , B （ ER ^＋ , and/or PR ^＋ , Her - 2/neu ^＋ ）, and C （ triple - negative ： ER ^- , PR ^- , and Her - 2/ neu- ）. Immunostained tissue biopsies were observed under a microscope, evaluated and scored using in- tensity （0, ＋ , ＋＋ , and ＋＋＋ ） and percentage of positive cells, and data were statistically analyzed. Re- suits Membranous E - eadherin was positive in all 57 cases （ 100% ）, whereas cytoplasmic E - cadherin was predominantly positive in groups B and C as compared with group A （21% , 7% , and 0% , respective- ly）. All cases in group A were negative for vimentin and EGFR. There was statistically increased expres- sion of vimentin, EGFR （ P 〈 0.01 ）, and NF - KB （ P 〈 0. 05 ） in triple - negative cases when compared with groups A and B. Conclusion Vimentin, EGFR, and NF - KB were significantly increased in triple - negative breast cancer, which is consistent with the invasiveness of these tumors.