Immunophenotyping invasive breast cancer: Paving the road for molecular imaging

Jeroen F. Vermeulen, Aram S.A. van Brussel, Petra van der Groep, Folkert H.M. Morsink, Peter Bult, Elsken van der Wall, Paul J. van Diest

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers.Methods: Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer.Results: The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status.Conclusions: In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

Original languageEnglish (US)
Article number240
JournalBMC cancer
Volume12
DOIs
StatePublished - Jun 13 2012
Externally publishedYes

Keywords

  • Antibody panel
  • Immunohistochemistry
  • Invasive breast cancer
  • Optical imaging
  • Tumor markers

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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