Separase is a marker for prognosis and mitotic activity in breast cancer

Br J Cancer. 2017 Oct 24;117(9):1383-1391. doi: 10.1038/bjc.2017.301. Epub 2017 Aug 31.


Background: Cancer cell proliferation is a critical feature in classifying and predicting the outcome of breast carcinoma. Separase has a central role in cell cycle progression in unleashing sister-chromatids at anaphase onset. Abnormally functioning separase is known to lead to chromosomal instability.

Methods: The study comprises 349 breast carcinoma patients treated in Central Hospital of Central Finland. The prognostic value, role as a proliferation marker and regulatory interactions of separase are evaluated by immunohistochemical and double- and triple-immunofluorescence (IF) detections based on complete clinical data and >22-year follow-up of the patient material.

Results: In our material, abnormal separase expression predicted doubled risk of breast cancer death (P<0.001). Up to 11.3-year survival difference was observed when comparing patients with and without separase expressing cancer cell mitoses. Particularly, abnormal separase expression predicted impaired survival for luminal breast carcinoma (P<0.001, respectively). In multivariate analyses, abnormal separase expression showed independent prognostic value. The complex inhibitory interactions involving securin and cyclin B1 were investigated in double- and triple-IFs and revealed patient subgroups with aberrant regulation and expression patterns of separase.

Conclusions: In our experience, separase is a promising and clinically applicable proliferation marker. Separase expression shows strong and independent prognostic value and could be developed into a biomarker for treatment decisions in breast carcinoma, particularly defining prognostic subgroups among luminal carcinomas.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Female
  • Humans
  • Mitosis / physiology*
  • Neoplasm Staging
  • Prognosis
  • Securin / metabolism*
  • Separase / metabolism*
  • Survival Rate


  • Biomarkers, Tumor
  • Securin
  • Separase