Shed HER2 surrogacy evaluation in primary breast cancer patients: a study assessing tumor tissue HER2 expression at both extracellular and intracellular levels

Abstract

The aim of the present study was to investigate serum HER2 extracellular domain (ECD) as a putative surrogate marker of the shedding phenomenon of HER2 receptor from the tumor tissue of primary breast cancer (BC) patients. A pilot retrospective study was conducted on 100 matched serum and tissue samples from patients with node-positive primary BC, stage II/III. Analysis of association and concordance between serum HER2 ECD levels (measured by chemiluminescence immunoassay) and the expression in matched tumor tissue of HER2 ECD and intracellular receptor domain (ICD) (determined by immunohistochemistry) were performed. The median serum HER2 ECD level was 9.4 ng/ml and cutoff values were set at 15.2 ng/ml or 13.0 ng/ml. HER2 ICD and ECD were overexpressed in tumor tissue of 19.8% and 6.9% of patients, respectively. Statistically significant associations were found between serum HER2 ECD levels and tissue expression of both HER2 ICD and ECD (p < .001; Fisher analysis). Moreover, strong concordances were found between serum HER2 ECD levels and tissue expression of HER2 ICD or ECD (cutoff 15.2 ng/ml: 80 and 92.5%, respectively). Our findings support a role for serum HER2 ECD as a surrogate marker of tissue HER2 status in primary BC, both for HER2 ICD or ECD expression.

Keywords:

• ErbB-2 receptor
• protein domains
• tumor biomarker
• serum
• breast neoplasms

Acknowledgments

The authors would like to thank Dr. Antonette E. Leon for her contribution in editing the manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with ‘The Code of Ethics of the World Medical Association (Declaration of Helsinki, 1964)’ and its later amendments or comparable ethical standards.

For this type of retrospective study formal consent was not required (written informed consent was not required by the local ethic committee for the use of data already collected for clinical purposes since confidentiality was guaranteed and no additional interventions were performed).

Disclosure statement.

The authors declare that they have no conflict of interest.

Additional information

Funding

This study was partially supported by grants from the Italian Association for Research on Cancer (AIRC), under Grant Special Program Molecular Clinical Oncology, 5x1000, No. 12214.