Different Expression Patterns of CXCR4, CCR7, Maspin and FOXP3 in Luminal Breast Cancers and Their Sentinel Node Metastases

Anticancer Res. 2017 Jan;37(1):175-182. doi: 10.21873/anticanres.11303.

Abstract

Aim: Luminal A breast cancers (BC) represent low-risk tumors conferring better outcome than luminal B and human epidermal growth factor 2 (HER2)-positive or triple-negative tumors. One reason for the heterogeneous outcome among patients with luminal BC is the variation in cell proliferation. As chemokine receptors and tumor suppressors show potential for estimation of infiltration to regional lymph nodes, we aimed to compare differently sized sentinel node metastases with their primary tumors (PT).

Materials and methods: We compared 29 BCs of luminal subtype A and 23 of subtype B (Ki-67 cut off at 14%) by immunohistochemistry for the chemokine receptors C-X-C chemokine receptor 4 (CXCR4), C-C-chemokine receptor 7 (CCR7), the tumor suppressor Maspin and the regulatory T-cell immunosuppressor forkhead box protein 3 (FOXP3) between PTs and their metastases of different size.

Results: Expression of CXCR4 was low in luminal A type tumors, and CCR7 and FOXP3 expression were high in luminal B type cancer. CXCR4 expression significantly positively correlated with CCR7 both in PTs and metastases. Most Maspin-positive PTs became negative in the metastases. The PTs for all Maspin-positive metastases were luminal B type.

Conclusion: High CXCR4 expression in PTs was found to be associated with luminal A type tumor, suggesting more favorable outcome. In contrast, CCR7 and FOXP3 expressions in PTs represented luminal B tumors, pointing to more aggressive tumor behavior. Maspin expression did not differ between luminal types.

Keywords: CCR7; CXCR4; FOXP3; Luminal breast cancer; Maspin; isolated tumor cells; micrometastasis; sentinel node.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Middle Aged
  • Receptors, CCR7 / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Serpins / metabolism*

Substances

  • CCR7 protein, human
  • CXCR4 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, CCR7
  • Receptors, CXCR4
  • SERPIN-B5
  • Serpins