p95-HER2 and trastuzumab resistance in metastatic breast cancer; is immunohistochemistry appropriate?

J BUON. 2014 Jan-Mar;19(1):245-9.

Abstract

Purpose: Unraveling the mechanisms underlying the resistance to trastuzumab is important for amending the prognosis of patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Experimentally, it has been shown that p95-HER2 positive breast tumors are resistant to trastuzumab. The aim of this study was to investigate the predictive and prognostic importance of p95-HER2 expression by immunohistochemistry in HER2-positive metastatic breast cancer patients treated with trastuzumab.

Methods: Only patients who had a histological diagnosis of HER2-positive metastatic breast cancer and who had received first line therapy containing trastuzumab were enrolled in the study. Immunohistochemistry was used to analyze p95-HER2 expression in the tissue blocks of the patients.

Results: The study was performed on 38 patients aged between 30 and 84 years. In 14 patients (36.8%), p95-HER2 was positive, whereas it was negative in the remaining 24 patients (63.2%). There was no significant correlation between p95-HER2 expression and overall survival, response to trastuzumab, and progression-free survival (PFS).

Conclusion: Unlike previous reports, there was no correlation between the p95-HER2 expression and resistance to trastuzumab. It may be argued that an analysis using immunohistochemistry is inadequate for determining p95- HER2. In order to ascertain whether immunohistochemistry is an appropriate method, studies with larger patient groups are needed.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins c-vav / biosynthesis*
  • Proto-Oncogene Proteins c-vav / genetics
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Proto-Oncogene Proteins c-vav
  • VAV1 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab