Increased tumor cell expression of Axl is a marker of aggressive features in breast cancer among African women

APMIS. 2015 Aug;123(8):688-96. doi: 10.1111/apm.12403. Epub 2015 May 25.

Abstract

Axl, a receptor tyrosine kinase belonging to the Tyro/Axl/Mer (TAM) family, has been shown to be overexpressed in breast cancer with poor outcome. Moreover, Axl was associated with a basal-like phenotype (BLP) in these tumors. Our aim was to investigate Axl expression in breast cancers from an African population since these tumors are known to be aggressive and have a high frequency of the basal-like phenotype. We studied 170 paraffin-embedded breast carcinoma cases by tissue microarrays and immunohistochemical methods. In total, 128 tumor cases (75%) had strong Axl expression and 42 cases (25%) had weak or negative staining. Strong expression of Axl was associated with high tumor grade (p < 0.0005), estrogen receptor (ER) negativity (p = 0.024), p53 expression (p = 0.004), P-cadherin positivity (p = 0.017), and basal-like phenotypic profiles BLP2 (p = 0.033) and BLP3 (p = 0.022). In addition, Axl overexpression also showed an association with markers of tumor cell proliferation and tumor angiogenesis. In conclusion, our findings indicate strong expression of Axl in a high proportion of breast cancer cases among African women and associations with markers of aggressive features, indicating poor prognosis. These findings suggest Axl as a potential therapeutic target in this population.

Keywords: Axl; Basal-like breast cancer; angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Black People / genetics
  • Breast Neoplasms / diagnosis*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Middle Aged
  • Neovascularization, Pathologic
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • Cadherins
  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human