High nuclear MSK1 is associated with longer survival in breast cancer patients.
PURPOSE
Mitogen- and stress-activated kinases (MSKs) are important substrates of the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1 and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being suggested to potentially play a role in breast cancer cell proliferation, cell cycle progression, cell migration, invasion and tumour growth. The aim of the current study was to assess MSK1 protein expression in breast cancer tumour specimens, evaluating its prognostic significance.


METHODS
A large cohort of 1902 early stage invasive breast cancer patients was used to explore the expression of MSK1. Protein expression was examined using standard immunohistochemistry on tissue microarrays.


RESULTS
Low MSK1 protein expression was associated with younger age (P = 0.004), higher tumour grade (P < 0.001), higher Nottingham Prognostic Index scores (P = 0.007), negative ER (P < 0.001) and PR (P < 0.001) status, and with triple-negative (P < 0.001) and basal-like (P < 0.001) phenotypes. Low MSK1 protein expression was significantly associated with shorter time to distant metastasis (P < 0.001), and recurrence (P = 0.013) and early death due to breast cancer (P = 0.01). This association between high MSK1 expression and improved breast cancer-specific survival was observed in the whole cohort (P = 0.009) and in the HER2-negative and non-basal like tumours (P = 0.006 and P = 0.024, respectively). Multivariate analysis including other prognostic variables indicated that MSK1 is not an independent marker of outcome.


CONCLUSIONS
High MSK1 is associated with improved breast cancer-specific survival in early stage invasive breast cancer patients, and has additional prognostic value in HER2-negative and non-basal like disease. Although not an independent marker of outcome, we believe such findings and significant associations with well-established negative prognostic factors (age, grade, Nottingham Prognostic Index, hormone receptor status, time to distant metastasis, recurrence and triple-negative/basal-like status) warrant further examination and validation in independent patient cohorts.
['Pu|Xuan|X|', 'Storr|Sarah J|SJ|', 'Ahmad|Narmeen S|NS|', 'Rakha|Emad A|EA|', 'Green|Andrew R|AR|', 'Ellis|Ian O|IO|', 'Martin|Stewart G|SG|http://orcid.org/0000-0002-2810-2338']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D001943:Breast Neoplasms D002467:Cell Nucleus D015331:Cohort Studies D005260:Female D006801:Humans D007150:Immunohistochemistry D008875:Middle Aged D011379:Prognosis D018719:Receptor, ErbB-2 D038744:Ribosomal Protein S6 Kinases, 90-kDa D016019:Survival Analysis
Breast cancer MSK Breast cancer-specific survival Biomarker