Correlation of total and phosphorylated HSP27 with HER2-positivity in breast cancer

Abstract

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is a highly aggressive subtype of breast cancer, found in around 20% of diagnosed breast cancer cases. The overexpression of the HER2 cell surface protein is associated with a poor prognosis, high recurrence and low survival rate. Over-expression of this receptor is routinely tested for in breast cancer classification and determination of eligibility for treatment with the monoclonal antibody trastuzumab (Herceptin®). Despite promising results in most patients, the presence of innate or acquired resistance to the drug is a well-documented hurdle of trastuzumab treatment. In previous studies, it has been indicated that a) an increased concentration of the heat shock protein 27 (HSP27) is associated with HER2-positive breast cancer and b) the presence of HSP27 phosphorylated at serine 78 (pHSP27ser78) in tumour cells may render them resistant to trastuzumab. Nonetheless, the involvement of HSP27 in HER2-positive breast cancer as well as its role in the resistance to trastuzumab are not yet fully understood. The aim of this study was to determine whether the expression of HSP27 and its phosphorylated portion pHSP27ser78 is indeed higher in HER2-positive breast cancer cells as opposed to HER2-negative tumours. Thus, 168 formalin-fixed paraffin embedded (FFPE) samples consisting of 89 HER2-positive cases and 79 HER2-negative controls were separately stained by immunohistochemistry with anti-HSP27and anti-pHSP27ser78 antibodies. The sections were then scored using the H-score and the difference in the scores of HER2-positive and HER2-negative samples was tested using statistical methods. It was determined that, while HER2-positive and HER2-negative tumours express similar amounts of total HSP27, the expression of pHSP27ser78 is significantly higher in HER2-positive tumours. This might contribute to the development of resistance to trastuzumab.