Breast Carcinoma-associated Fibroblasts Share Similar Biomarker Profiles in Matched Lymph Node Metastasis

Breast Carcinoma-associated Fibroblasts Share Similar Biomarker Profiles in Matched Lymph Node Metastasis

Author Mundim, Fiorita Gonzales Lopes Autor UNIFESP Google Scholar
Pasini, Fatima S. Google Scholar
Nonogaki, Suely Google Scholar
Rocha, Rafael M. Google Scholar
Soares, Fernando A. Google Scholar
Brentani, Maria M. Google Scholar
Logullo, Angela Flavia Autor UNIFESP Google Scholar
Abstract This study sought to understand the role of breast carcinoma-associated fibroblasts in the progression of cancer cells into lymph nodes. We compared fibroblasts of primary tumors and matched the involved lymph nodes to select fibroblast activation markers, namely -smooth muscle actin (-SMA), S100A4, and vimentin, as well as to determine the frequency of transforming growth factor 1, a pleiotropic cytokine that induces the differentiation of fibroblasts to myofibroblasts, and its downstream effectors: CXCR4 and p-AKT. We disposed samples of 80 primary invasive ductal carcinomas and matched the involved lymph nodes from 43 cases into 3 tissue microarrays, and analyzed stromal and tumor epithelial cells separately by immunohistochemistry. Control uninvolved lymph nodes were analyzed by whole-tissue sections. Cancer-associated fibroblast in lymph nodes with macrometastasis expressed similar profiles of vimentin, -SMA, and S100A4 as those found in primary tumors. Cancer-associated fibroblast were uniformly estrogen receptor, progesterone receptor, HER-2, Ki-67, and p53 negative, but expressions of transforming growth factor 1 (TGF1), CXCR4, and p-AKT staining (62.3%, 52.4%, 65%, respectively) were equivalent between primary and lymph node metastasis (LNM) fibroblasts. A significant coexpression of TGF1 with p-AKT and CXCR4 in LNMs suggested the involvement of these proteins with TGF1 signaling. These biomarkers, including -SMA and S100A4, were negative in fibroblasts of cancer-free lymph nodes, with the exception of vimentin. Our finding that expressions of biological markers were similar in fibroblasts of the primary tumors and in matched LNMs, but were absent in cancer-free lymph nodes, supports the assumption that the lymph node stroma mimics the microenvironment observed in primary tumors.
Keywords breast carcinoma
cancer-associated fibroblasts
nodal metastases
invasion markers
xmlui.dri2xhtml.METS-1.0.item-coverage Philadelphia
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 09/10088-7
Date 2016
Published in Applied Immunohistochemistry & Molecular Morphology. Philadelphia, v. 24, n. 10, p. 712-720, 2016.
ISSN 1541-2016 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 712-720
Access rights Closed access
Type Article
Web of Science ID WOS:000388964200008

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