Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis
Introduction: The identification of tumor cells that can be potential metastatic seeds would reach two key aims—prognosis of metastasis risk and appointment of the optimal adjuvant therapy to prevent metastatic disease. Single tumor cells (STCs) located out of multicellular structures can most likel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00050/full |
| _version_ | 1818162965839347712 |
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| author | Liubov A. Tashireva Marina V. Zavyalova Marina V. Zavyalova Olga E. Savelieva Tatyana S. Gerashchenko Evgeniya V. Kaigorodova Evgeniya V. Kaigorodova Evgeny V. Denisov Evgeny V. Denisov Vladimir M. Perelmuter |
| author_facet | Liubov A. Tashireva Marina V. Zavyalova Marina V. Zavyalova Olga E. Savelieva Tatyana S. Gerashchenko Evgeniya V. Kaigorodova Evgeniya V. Kaigorodova Evgeny V. Denisov Evgeny V. Denisov Vladimir M. Perelmuter |
| author_sort | Liubov A. Tashireva |
| collection | DOAJ |
| description | Introduction: The identification of tumor cells that can be potential metastatic seeds would reach two key aims—prognosis of metastasis risk and appointment of the optimal adjuvant therapy to prevent metastatic disease. Single tumor cells (STCs) located out of multicellular structures can most likely demonstrate features that are needed to initiate metastasis.Methods: One-hundred-and-thirty-five patients with invasive breast carcinoma of no special type have been enrolled. Molecular subtypes of breast cancer were categorized according to St. Gallen recommendations. Hematoxylin and eosin staining was used to identify STCs with epithelial-like morphology (eSTCs) in breast tumors. Immunofluorescence staining was applied to evaluate stemness and epithelial–mesenchymal transition (EMT) in STCs. The correlation between STCs and recurrence and metastasis-free survival (MFS) was performed using the Kaplan–Meier method and the log-rank test.Results: Distant metastasis was more frequent in eSTC-positive than eSTC-negative patients (28.0% vs. 9.4%, p = 0.007). When tumor types were analyzed separately, distant metastasis tended to be more frequent in eSTC-positive than eSTC-negative patients for HER2-positive cancer [75.0% (3/4) vs. 12.5% (1/8), p = 0.066]. In luminal A [22.7% (5/22) vs. 10.0% (3/30), p = 0.259], luminal B [21.1% (4/19) vs. 6.7% (2/30), p = 0.189], and triple-negative [40.0% (2/5) vs. 11.8% (2/17), p = 0.209] cancers, distance metastasis was not associated with eSTCs. Median MFS was not reached in eSTC-positive and eSTC-negative patients. eSTC-positive patients had a higher risk of breast cancer metastasis [hazard ratio (HR) 3.57, 95% confidence interval (CI): 1.46–8.71; p = 0.001]. When tumor types were analyzed separately, a higher risk of breast cancer metastasis occurred only in HER2-positive patients (HR 8.49, 95% CI: 1.29–55.59; p = 0.016). Immunofluorescence analysis revealed mesenchymal-like STCs (mSTCs) and inter- and intra-tumor heterogeneity in STCs. There were breast tumors with either eSTCs or mSTCs and tumors with both types of STCs. Both eSTCs and mSTCs were represented by cells with different stem and/or EMT phenotypes.Conclusions: STCs with epithelial-like morphology contribute to breast cancer metastasis and represent an attractive model for studying mechanisms of metastatic seeding. The assessment of STCs in histological sections of breast tumors can be a simple and effective method for the prediction of metastasis risk. |
| first_indexed | 2024-12-11T16:42:03Z |
| format | Article |
| id | doaj.art-fe4324cbcc224f2fa803179a49806cd3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T16:42:03Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-fe4324cbcc224f2fa803179a49806cd32022-12-22T00:58:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00050492802Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer MetastasisLiubov A. Tashireva0Marina V. Zavyalova1Marina V. Zavyalova2Olga E. Savelieva3Tatyana S. Gerashchenko4Evgeniya V. Kaigorodova5Evgeniya V. Kaigorodova6Evgeny V. Denisov7Evgeny V. Denisov8Vladimir M. Perelmuter9Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaDepartment of Pathological Anatomy, Siberian State Medical University, Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaDepartment of Biochemistry and Molecular Biology, Siberian State Medical University, Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaDepartment of Organic Chemistry, Tomsk State University, Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, RussiaIntroduction: The identification of tumor cells that can be potential metastatic seeds would reach two key aims—prognosis of metastasis risk and appointment of the optimal adjuvant therapy to prevent metastatic disease. Single tumor cells (STCs) located out of multicellular structures can most likely demonstrate features that are needed to initiate metastasis.Methods: One-hundred-and-thirty-five patients with invasive breast carcinoma of no special type have been enrolled. Molecular subtypes of breast cancer were categorized according to St. Gallen recommendations. Hematoxylin and eosin staining was used to identify STCs with epithelial-like morphology (eSTCs) in breast tumors. Immunofluorescence staining was applied to evaluate stemness and epithelial–mesenchymal transition (EMT) in STCs. The correlation between STCs and recurrence and metastasis-free survival (MFS) was performed using the Kaplan–Meier method and the log-rank test.Results: Distant metastasis was more frequent in eSTC-positive than eSTC-negative patients (28.0% vs. 9.4%, p = 0.007). When tumor types were analyzed separately, distant metastasis tended to be more frequent in eSTC-positive than eSTC-negative patients for HER2-positive cancer [75.0% (3/4) vs. 12.5% (1/8), p = 0.066]. In luminal A [22.7% (5/22) vs. 10.0% (3/30), p = 0.259], luminal B [21.1% (4/19) vs. 6.7% (2/30), p = 0.189], and triple-negative [40.0% (2/5) vs. 11.8% (2/17), p = 0.209] cancers, distance metastasis was not associated with eSTCs. Median MFS was not reached in eSTC-positive and eSTC-negative patients. eSTC-positive patients had a higher risk of breast cancer metastasis [hazard ratio (HR) 3.57, 95% confidence interval (CI): 1.46–8.71; p = 0.001]. When tumor types were analyzed separately, a higher risk of breast cancer metastasis occurred only in HER2-positive patients (HR 8.49, 95% CI: 1.29–55.59; p = 0.016). Immunofluorescence analysis revealed mesenchymal-like STCs (mSTCs) and inter- and intra-tumor heterogeneity in STCs. There were breast tumors with either eSTCs or mSTCs and tumors with both types of STCs. Both eSTCs and mSTCs were represented by cells with different stem and/or EMT phenotypes.Conclusions: STCs with epithelial-like morphology contribute to breast cancer metastasis and represent an attractive model for studying mechanisms of metastatic seeding. The assessment of STCs in histological sections of breast tumors can be a simple and effective method for the prediction of metastasis risk.https://www.frontiersin.org/article/10.3389/fonc.2020.00050/fullsingle tumor cellsbreast cancerEMTstem celldistant metastasis |
| spellingShingle | Liubov A. Tashireva Marina V. Zavyalova Marina V. Zavyalova Olga E. Savelieva Tatyana S. Gerashchenko Evgeniya V. Kaigorodova Evgeniya V. Kaigorodova Evgeny V. Denisov Evgeny V. Denisov Vladimir M. Perelmuter Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis Frontiers in Oncology single tumor cells breast cancer EMT stem cell distant metastasis |
| title | Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis |
| title_full | Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis |
| title_fullStr | Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis |
| title_full_unstemmed | Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis |
| title_short | Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis |
| title_sort | single tumor cells with epithelial like morphology are associated with breast cancer metastasis |
| topic | single tumor cells breast cancer EMT stem cell distant metastasis |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00050/full |
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