Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer.

M Mego,M Mego,M Mego,G Minarik,J Mardiak,L Danihel,T Sedlácková,Jm Reuben,G Sieberova,P Gronesova,Z Cierna,P Janega,D Manasova,P Gronesova,M Karaba,J Mardiak,J Benca,J Mardiak,D Pindak,J Sufliarsky

doi:10.1186/s12885-015-1548-7

Abstract

BackgroundCirculating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue.MethodsThis study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score.ResultsCTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT.ConclusionsIn this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features.

Highlights

Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients
Increased number of studies demonstrated that cancer cells often undergo epithelial to mesenchymal transition (EMT), to acquire the traits needed to execute the multiple steps of metastasis [6]
CTCs with only epithelial markers were present in peripheral blood of 9 (8.8 %) patients; CTC with Epithelial to mesenchymal transition (EMT) only phenotype were present in 13 (12.8 %) of patients; in 3 (2.9 %) of patients CTCs exhibited both epithelial and mesenchymal markers (Table 2)

Summary

Introduction

Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) have a crucial role in the metastatic cascade, tumor dissemination and progression. Prognostic value of CTCs was demonstrated by numerous trials for metastatic as well as primary breast cancer [1,2,3,4]. To successfully execute the metastatic cascade, epithelial tumor cells must detach from the primary tumor, pass through the peripheral circulation, extravasate at the distant site and establish a new tumor. Increased number of studies demonstrated that cancer cells often undergo epithelial to mesenchymal transition (EMT), to acquire the traits needed to execute the multiple steps of metastasis [6].

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