Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas

Anticancer Res. 2018 Apr;38(4):1957-1965. doi: 10.21873/anticanres.12433.

Abstract

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs.

Keywords: Podoplanin-positive cancer-associated fibroblasts; lymph node metastases; primary tumor; prognostic significance.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Membrane Glycoproteins / biosynthesis*
  • Neoplasms, Multiple Primary / metabolism*
  • Neoplasms, Multiple Primary / pathology*
  • Receptor, ErbB-2 / biosynthesis*
  • Retrospective Studies
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • Membrane Glycoproteins
  • PDPN protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2