Abstract
Background: Targeted image-guided surgery is based on the detection of tumor cells after administration of a radio-active or fluorescent tracer. Hence, enhanced binding of a tracer to tumor tissue compared to healthy tissue is crucial. Various tumor antigens have been evaluated as possible targets for image-guided surgery of breast cancer, with mixed results. Methods: In this study we have evaluated tyrosine kinase receptor EphB4, a member from the Eph tyrosine kinase receptor family, as a possible target for image-guided surgery of breast cancers. Two independent tissue micro arrays, consisting of matched sets of tumor and normal breast tissue, were stained for EphB4 by immunohistochemistry. The intensity of staining and the percentage of stained cells were scored by two independent investigators. Results: Immunohistochemical staining for EphB4 shows that breast cancer cells display enhanced membranous expression compared to adjacent normal breast tissue. The enhanced tumor staining is not associated with clinical variables like age of the patient or stage or subtype of the tumor, including Her2-status. Conclusion: These data suggest that EphB4 is a promising candidate for targeted image-guided surgery of breast cancer, especially for Her2 negative cases.
Highlights
Breast cancer is the most commonly diagnosed cancer in women in Europe with an incidence of 523,000 new cases every year and is the third leading cause of death from cancer with 135,000 women every year [1]
Irrespective of the type of antibody used, immunohistochemical staining for EphB4 was primarily present in tumor cells throughout the tumor tissue cores
EphB4 staining was prominently observed on the membrane and in the cytoplasm of the cells and occasionally in the nucleus (Figure 1)
Summary
Breast cancer is the most commonly diagnosed cancer in women in Europe with an incidence of 523,000 new cases every year and is the third leading cause of death from cancer with 135,000 women every year [1]. Methods of tumor boundary assessment vary from traditional tactile information, wire-guided localization, and analysis of frozen biopsies to advanced imaging technologies such as intraoperative positron emission tomography (PET) imaging and optical coherence tomography [2,5]. All these modalities have their limitations and none has yet proved to outperform the others. Methods: In this study we have evaluated tyrosine kinase receptor EphB4, a member from the Eph tyrosine kinase receptor family, as a possible target for image-guided surgery of breast cancers. Results: Immunohistochemical staining for EphB4 shows that breast cancer cells display enhanced membranous expression compared to adjacent normal breast tissue. Conclusion: These data suggest that EphB4 is a promising candidate for targeted image-guided surgery of breast cancer, especially for Her negative cases
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