Abstract:

Objective To detect the levels of different phenotypic circulating tumor cells（CTCs） in patients with metastatic breast cancer（MBC） and discuss the predictive significance of CTCs on curative effect. Methods We detected the expression of epithelial（CK18， CK19） and mesenchymal（vimentin，fibronectin） markers in CTCs from 58 MBC patients and 10 healthy people by magnetic activated cell sorting（MACS） technology combined with RT-PCR. Curative effect of chemotherapy in MBC patients with different CTCs subgroups was evaluated using RECIST criteria. ResultsThere was no positive expression of CK18， CK19, vimentin and fibronectin mRNA in blood samples from 10 healthy volunteers. Among 58 MBC samples，62.1％（36／58） was found to express the CKs epithelial markers and 32.8％（19／58） were found to express the mesenchymal markers. In three different breast cancer subgroups， the positive rate of epithelial markers in luminal A and HER-2 positive subgroups higher than that in the triple negative subgroups（P=0.008）. However， the expression of the mesenchymal markers was observed to be reversed（P＜0.001）. Based on the expression of epithelial（CKs） and mesenchymal（EMT） markers in CTCs， the patients could be divided into CKs+／EMT- group, CKs-／EMT- group, CKs+／EMT+ group and CKs-／EMT+ group. The response rates of 4 group were 76.7%, 55.6%, 33.3% and 15.4%, respectively. There was significant difference（P＜0.05）. After two cycles of chemotherapy，the overall response rate（ORR） of EMT+ patients was lower than that of EMT- patients（15.8% vs. 71.8%, P=0.000）. Conclusion Some CTCs undergo EMT and subsequently lose their epithelial markers， such as cytokeratins， and gain the mesenchymal markers， such as vimentin and fibronectin. The presence of mesenchymal CTCs predicted resistance to chemotherapy and they maybe one of the reasons of invalid therapy of triple negative breast cancer.