Evaluation of human epididymal secretory protein 4 expression according to the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-positive, triple-negative) of breast cancer

Indian J Pathol Microbiol. 2018 Jul-Sep;61(3):323-329. doi: 10.4103/IJPM.IJPM_465_17.

Abstract

Background/aims: Human epididymal secretory protein 4 (HE4) is originally described as an epididymis-specific protein but more recently suggested to be a putative serum tumor marker for some tumors, including breast carcinomas. In this study, we aimed to investigate the interactions between HE4 expression and molecular subtypes of breast carcinomas.

Methods: HE4 expressions were studied in 242 formalin-fixed, paraffin-embedded breast carcinoma specimens and their association with different pathological and clinical parameters was evaluated.

Results: Immunohistochemical (IHC) staining for HE4 was negative in 3 (1.2%) cases, weakly positive (1+) in 7 (2.9%) cases, moderately positive (2+) in 58 (24.0%) cases, and strongly positive (3+) in 174 (71.9%) cases. A correlation between IHC HE4 staining grade and molecular groups was detected (P = 0.005). Furthermore, it was found that HE4 expression was strongly associated with histological tumor grade, c-erbB2 expression, and positive fluorescence in situ hybridization test results that detect human epidermal growth factor receptor 2 (HER2)/neu amplification (P = 0.022, P = 0.014, and P = 0.011).

Conclusion: This study showed that HE4 expression is associated with HER2/neu amplification in breast cancers. These results may be commented as HE4 expression rises in patients with HER2/neu amplification. As is known, HER2/neu amplification is a poor diagnostic factor in breast cancer and HE4 expression is possibly associated with poor prognosis.

Keywords: Breast cancer; human epididymal secretory protein 4; immunohistochemistry; molecular groups.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / classification*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Genes, erbB-2 / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence / methods
  • Middle Aged
  • Proteins / genetics*
  • Receptor, ErbB-2 / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • WAP Four-Disulfide Core Domain Protein 2

Substances

  • Biomarkers, Tumor
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2