Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast

Histopathology. 2009 May;54(6):741-50. doi: 10.1111/j.1365-2559.2009.03289.x.

Abstract

Aims: Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread.

Methods and results: We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes (P < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC (P = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC (P = 0.007) and correlated significantly with lymph node status (P = 0.002), although SDF-1 mRNA was rarely detected by CISH.

Conclusions: This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology*
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • Tissue Array Analysis

Substances

  • Chemokine CXCL12
  • Receptors, CXCR4