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Increased expression of senescence markers p14(ARF) and p16 (INK) (4a) in breast cancer is associated with increased risk of disease recurrence and poor survival outcome.
Pare R, et al. Histopathology. 2016.
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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. This study aimed to characterize the expression patterns of senescence markers p14(ARF) , p16(INK) (4a) and p21(WAF) (1/Cip1) during breast cancer progression in a large patient cohort.

METHODS AND RESULTS: 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 include normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient. Invasive ductal carcinomas demonstrated greater expression of p14(ARF) and p16(INK) (4a) , but lower expression of p21(WAF) (1/Cip1) when compared to non-malignant tissues. There was significant correlation between normal, benign, pre-invasive and malignant tissues with p14(ARF) , p16(INK) (4a) and p21 (WAF) (1/Cip1) expression (p<0.05). Univariate comparison showed correlation between strong p16(INK) (4a) expression with poor survival (p=0.000) and increased risk of relapse (p=0.000), while high p14(ARF) expression correlated only with increased risk of relapse (p=0.038). Multivariate analysis showed p16(INK) (4a) as an important prognostic factor for overall survival (p=0.011) and disease free survival (p=0.004), with p14(ARF) also a significant prognostic factor for disease free survival (p=0.043). Moreover, patients displaying both strong p16 and p14 expressions had an adjusted 3-fold increased risk of disease recurrence (p<0.05) and 2-fold increased risk of all-cause related death (p<0.05).

CONCLUSIONS: These finding suggest p16(INK) (4a) 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. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
PMID 26843058 [PubMed - as supplied by publisher]
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شنبه, 04 ارديبهشت 1395 16:53 چاپ

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