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Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series

Azevedo Koike Folgueira, M. A., Maistro, S., Hirata Katayama, M. L., Roela, R. A., Lopes Mundim, F. G., Nanogaki, S., de Bock, G. H. & Brentani, M. M., 2013, In : Bioscience reports. 33, p. 921-929 9 p., 00085.

Research output: Contribution to journalReview articleAcademicpeer-review

  • Maria Aparecida Azevedo Koike Folgueira
  • Simone Maistro
  • Maria Lucia Hirata Katayama
  • Rosimeire Aparecida Roela
  • Fiorita Gonzales Lopes Mundim
  • Suely Nanogaki
  • Geertruida H. de Bock
  • M. Mitzi Brentani

CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: 'breast cancer' and 'lymph node' and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside-binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types.

Original languageEnglish
Article number00085
Pages (from-to)921-929
Number of pages9
JournalBioscience reports
Volume33
Publication statusPublished - 2013

    Keywords

  • breast cancer, cancer-associated fibroblasts, caveolin 1, lymph node metastasis, MMP13, podoplanin, INVASIVE DUCTAL CARCINOMA, GENE-EXPRESSION PROFILES, PROGNOSTIC-SIGNIFICANCE, PROLIFERATIVE ACTIVITY, PLASMINOGEN-ACTIVATOR, CAVEOLIN-1 EXPRESSION, TENASCIN-C, IN-SITU, CELLS, PODOPLANIN

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