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BMC Cancer. 2012; 12: 240.
Published online Jun 13, 2012. doi:  10.1186/1471-2407-12-240
PMCID: PMC3430576
Immunophenotyping invasive breast cancer: paving the road for molecular imaging
Jeroen F Vermeulen,1 Aram SA van Brussel,1 Petra van der Groep,2 Folkert HM Morsink,1 Peter Bult,3 Elsken van der Wall,2 and Paul J van Diestcorresponding author1
1Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
2Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands
3Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
corresponding authorCorresponding author.
Jeroen F Vermeulen: j.f.vermeulen-2/at/umcutrecht.nl; Aram SA van Brussel: a.s.a.vanbrussel-3/at/umcutrecht.nl; Petra van der Groep: p.vandergroep/at/umcutrecht.nl; Folkert HM Morsink: f.h.m.morsink/at/umcutrecht.nl; Peter Bult: p.bult/at/pathol.umcn.nl; Elsken van der Wall: e.vanderwall/at/umcutrecht.nl; Paul J van Diest: p.j.vandiest/at/umcutrecht.nl
Received January 6, 2012; Accepted May 31, 2012.
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.
Keywords: Invasive breast cancer, Tumor markers, Optical imaging, Immunohistochemistry, Antibody panel
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