Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers

PLoS One. 2017 Dec 15;12(12):e0189641. doi: 10.1371/journal.pone.0189641. eCollection 2017.

Abstract

Background: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers.

Methods: Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation.

Results: Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065).

Conclusion: We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • CA-125 Antigen / blood
  • Early Detection of Cancer*
  • Female
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Leptin / blood
  • Middle Aged
  • Mutation
  • Osteopontin / blood
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prolactin / blood

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Leptin
  • SPP1 protein, human
  • human epithelial antigen-125
  • Osteopontin
  • Insulin-Like Growth Factor II
  • Prolactin

Grants and funding

The authors received a study grant from the Austrian Society of Endocrinological Oncology (OEGEO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.