Increased expression of senescence markers p14(ARF) and p16(INK4a) in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome.
Histopathology
; 69(3): 479-91, 2016 Sep.
Article
em En
| MEDLINE
| ID: mdl-26843058
ABSTRACT
AIMS:
Breast cancer is a hormonally driven disease. Cellular senescence is an age-related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) during breast cancer progression in a large patient cohort. METHODS ANDRESULTS:
We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11-year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14(ARF) and p16(INK4a) but lower expression of p21(WAF1/Cip1) than non-malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) expression (P < 0.05). Univariate comparison showed a correlation between high p16(INK4a) expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14(ARF) expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16(INK4a) to be an important prognostic factor for overall survival (P = 0.011) and disease-free survival (P = 0.004), with p14(ARF) also being a significant prognostic factor for disease-free survival (P = 0.043). Moreover, patients showing both high p16(INK4a) expression and and high p14(ARF) expression had an adjusted three-fold increased risk of disease recurrence (P < 0.05) and a two-fold increased risk of all-cause-related death (P < 0.05).CONCLUSIONS:
These finding suggest p16(INK4a) expression and p14(ARF) expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Senescência Celular
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Carcinoma Ductal de Mama
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Inibidor p16 de Quinase Dependente de Ciclina
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Proteína Supressora de Tumor p14ARF
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article