Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer

Aleksandra Markiewicz,Barbara Seroczyńska,Jolanta Szade,Anna Zaczek,Magdalena Książkiewicz,Marzena Wełnicka-Jaśkiewicz,Jarosław Skokowski

doi:10.3390/cancers5041485

Aleksandra Markiewicz, Barbara Seroczyńska + Show 5 more

Open Access

https://doi.org/10.3390/cancers5041485

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Abstract

Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination.

Highlights

Metastatic spread still remains the main cause of deaths in breast cancer
Since epithelial-mesenchymal transition (EMT) was shown to play critical role in cancer dissemination, we focused on gene expression profiles related to lymphatic and hematogenous dissemination
We have found that examined profile of primary tumors (PT) did not correlate with hematogenous spread expressed as positivity either for circulating tumor cells (CTCs) epithelial (CK19+) or mesenchymal (VIM+) phenotype or CK19+ and/or MGB1+ and/or HER2+

Summary

Introduction

Metastatic spread still remains the main cause of deaths in breast cancer. There are two main routes of cancer cells dissemination in breast cancer: lymphatic and hematogenous.Axillary lymph node status is one of the most important prognostic factors for survival in breast cancer [1]. Clinical studies have shown that approximately 25% of patients with negative lymph node status still develop systemic recurrence and die of the disease [2,3,4]. This might suggest that hematogenous spread occurs in a substantial number of patients and is independent of lymphatic involvement. CTCs may constitute seeds for subsequent growth of metastasis in distant organs, according to Paget’s “seed and soil hypothesis” [15] They represent a heterogeneous population of tumor cells and only some of them are capable of developing metastasis

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Discussion

Conclusion