A1 Refereed original research article in a scientific journal
Separase is a marker for prognosis and mitotic activity in breast cancer
Authors: Gurvits N, Loyttyniemi E, Nykanen M, Kuopio T, Kronqvist P, Talvinen K
Publisher: NATURE PUBLISHING GROUP
Publication year: 2017
Journal: British Journal of Cancer
Journal name in source: BRITISH JOURNAL OF CANCER
Journal acronym: BRIT J CANCER
Volume: 117
Issue: 9
First page : 1383
Last page: 1391
Number of pages: 9
ISSN: 0007-0920
eISSN: 1532-1827
DOI: https://doi.org/10.1038/bjc.2017.301
Abstract
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.
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.
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