Differential expression of growth factor receptors and membrane-bound tumor markers for imaging in male and female breast cancer

PLoS One. 2013;8(1):e53353. doi: 10.1371/journal.pone.0053353. Epub 2013 Jan 4.

Abstract

Introduction: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer.

Methods: Tissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers.

Results: Growth factor receptors were variably expressed in 4.5% (MET) up to 38.5% (IGF1-R) of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII) were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers.

Conclusions: Expression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of molecular tracers for male breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms, Male / diagnosis
  • Breast Neoplasms, Male / genetics*
  • Carbonic Anhydrases / genetics*
  • Female
  • Gene Expression
  • Glucose Transporter Type 1 / genetics*
  • Gynecomastia / diagnosis
  • Gynecomastia / genetics*
  • Humans
  • Hyaluronan Receptors / genetics*
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Middle Aged
  • Molecular Imaging / standards
  • Receptors, Growth Factor / genetics*
  • Sex Factors
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • CD44v6 antigen
  • Glucose Transporter Type 1
  • Hyaluronan Receptors
  • Receptors, Growth Factor
  • SLC2A1 protein, human
  • Insulin-Like Growth Factor I
  • Carbonic Anhydrases
  • carbonic anhydrase XII

Grants and funding

This work was supported by an unrestricted research grant of AEGON Inc. and by the MAMmary carcinoma MOlecular imaging for diagnostics and THerapeutics (MAMMOTH) project of the Dutch Center for Translational Molecular Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.