Expression of proteins involved in DNA damage response in familial and sporadic breast cancer patients.
By: Giulia Partipilo, Giovanni Simone, Anna Scattone, Emanuela Scarpi, Amalia Azzariti, Anita Mangia

Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", viale Orazio Flacco 65, 70124, Bari, Italy.
2015-4-30; doi: 10.1002/ijc.29699
Abstract

Understanding the expression of proteins involved in DNA-damage response could improve knowledge of the pathways that contribute to familial and sporadic breast cancer. We aimed to assess the different role of BRCA1, Poly (ADP-ribose) polymerase-1 (PARP1), BRCT-repeat inhibitor of hTERT expression (BRIT1) and novel SWItch 5 (SWI5) expression in 130 sporadic and 73 familial breast cancer samples, by immunohistochemistry. In the sporadic group, negative nuclear BRCA1 (nBRCA1) expression was associated with positive PgR (p=0.037). Negative association was found between nBRCA1 expression and HER2 (p=0.001). In the familial group, nBRCA1 expression was associated with ER (p=0.002). Reduced nBRCA1 expression was associated with higher histological grade and positive Ki67 both in sporadic (p=0.0010, p=0.047) and familial groups (p<0.001, p=0.001). Nuclear PARP1 (nPARP1) expression was associated with histological grade (p=0.035) and positive PgR (p=0.047) in sporadic cases. High cytoplasmic and low nuclear BRIT1 (cBRIT1 and nBRIT1) expression were associated with high histological grade in the familial group (p=0.013, p=0.025). Various statistical associations between the protein expressions were observed in the sporadic group, while in familial group only few associations were found. Univariate analyses showed that nPARP1 expression is able to discriminate between sporadic and familial tumours (OR 2.80, p=0.002). Multivariate analyses proved that its overexpression is an independent factor associated with a high risk of sporadic tumour (OR 2.96, p=0.017). Our findings indicate that nPARP1 expression is an independent factor for sporadic breast cancers and PARP1 inhibitors could be a promising therapy for different phenotypes. This article is protected by copyright. All rights reserved.



© 2015 UICC.

PMID:26205471






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