Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Immunophenotyping invasive breast cancer: paving the road for molecular imaging

Jeroen F Vermeulen1, Aram SA van Brussel1, Petra van der Groep2, Folkert HM Morsink1, Peter Bult3, Elsken van der Wall2 and Paul J van Diest1*

Author Affiliations

1 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

2 Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands

3 Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

For all author emails, please log on.

BMC Cancer 2012, 12:240  doi:10.1186/1471-2407-12-240

Published: 13 June 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