Digital imaging-assisted quantification of H3K27me3 immunoexpression in luminal A/B-like, HER2-negative, invasive breast cancer predicts patient survival and risk of recurrence

Autor: João Lobo, Silvana Lobo, Sofia Salta, Susana Palma de Sousa, Mário Fontes-Sousa, Carmen Jerónimo, Paula Lopes, Luís Antunes, Rui Henrique, Maria Amorim
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
H3K27me3
Kaplan-Meier Estimate
Histones
0302 clinical medicine
Breast cancer
Medicine
lcsh:QD415-436
Precision Medicine
Genetics (clinical)
Middle Aged
Prognosis
030220 oncology & carcinogenesis
Cohort
Molecular Medicine
Female
Epigenetics
Research Article
medicine.medical_specialty
Down-Regulation
Breast Neoplasms
Methylation
Disease-Free Survival
lcsh:Biochemistry
03 medical and health sciences
Statistical significance
Internal medicine
Image Interpretation
Computer-Assisted
Genetics
Biomarkers
Tumor
Humans
Molecular Biology
Survival analysis
Neoplasm Staging
Receiver operating characteristic
business.industry
Proportional hazards model
lcsh:RM1-950
Histone mark
Luminal a
medicine.disease
Molecular medicine
030104 developmental biology
lcsh:Therapeutics. Pharmacology
Neoplasm Recurrence
Local
business
Software
Biomarkers
Zdroj: Molecular Medicine, Vol 26, Iss 1, Pp 1-9 (2020)
Molecular Medicine
ISSN: 1528-3658
1076-1551
Popis: Background Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness. Methods H3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as ‘low’ or ‘high’ expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis. Results The patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066–3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004–3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed (p = 0.069), reaching statistical significance in younger patients (p = 0.021). Conclusions H3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.
Databáze: OpenAIRE
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