Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair.

Abstract:

BACKGROUND:P38 mitogen activated protein kinase is an intermediary signal transduction factor with context-specific roles in breast cancer. Recent mechanistic studies add to the growing consensus that P38 is a tumour suppressor, and it may represent a novel target for breast cancer treatment. The aim of this study is to add definitive data on the prognostic value of P38 and its link with biomarkers in primary breast cancer. METHODS:A large, well-characterised series of 1332 primary breast cancer patients with long-term clinical follow-up was assessed for P38 expression by immunohistochemistry. Association of clinicopathological factors and a panel of breast cancer biomarkers was determined by chi-squared test, and multivariate survival analysis was performed using Cox Proportional Hazards regression modelling. RESULTS:This study shows that nuclear P38 is co-expressed with nuclear hormone receptors (p < 0.001) and is an independent prognostic marker of good long-term clinical outcome in primary breast cancer (hazard ratio 0.796, 95% confidence interval 0.662-0.957, p = 0.015). Significant association was found between expression of P38 and markers of DNA repair including nuclear BRCA1 and RAD51, and cleaved PARP1 (all p < 0.001). CONCLUSIONS:The findings support the proposed role for P38 as a tumour suppressor in breast cancer via upregulation of DNA repair proteins and provide novel hypothesis-generating information on the potential role of P38 in adjuvant therapy decision making.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Johnston SJ,Ahmad D,Aleskandarany MA,Kurozumi S,Nolan CC,Diez-Rodriguez M,Green AR,Rakha EA

doi

10.1186/s12885-018-4924-2

subject

Has Abstract

pub_date

2018-10-23 00:00:00

pages

1027

issue

1

issn

1471-2407

pii

10.1186/s12885-018-4924-2

journal_volume

18

pub_type

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