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Open Access Research article

53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA 19–9 in pancreatic adenocarcinoma

Natalie L Ausborn1, Tong Wang1, Sabrina C Wentz2, Mary Kay Washington2, Nipun B Merchant3, Zhiguo Zhao4, Yu Shyr4, Anuradha Bapsi Chakravarthy1 and Fen Xia5*

Author Affiliations

1 Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN, USA

2 Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, USA

3 Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA

4 Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA

5 Department of Radiation Oncology, The Ohio State University College of Medicine, Starling Loving, 300 W 10th Avenue, Columbus, OH, 43210, USA

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BMC Cancer 2013, 13:155  doi:10.1186/1471-2407-13-155

Published: 26 March 2013

Abstract

Background

53BP1 binds to the tumor suppressor p53 and has a key role in DNA damage response and repair. Low 53BP1 expression has been associated with decreased survival in breast cancer and has been shown to interact with several prognostic factors in non-small cell lung cancer. The role of 53BP1 in pancreatic ductal adenocarcinoma (PDAC) has yet to be determined. We aimed to investigate whether 53BP1 levels interact with established prognostic factors in PDAC.

Methods

106 patients for whom there was tissue available at time of surgical resection for PDAC were included. A tissue microarray was constructed using surgical specimens, stained with antibodies to 53BP1, and scored for expression intensity. Univariate and multivariate statistical analyses were performed to investigate the association between 53BP1 and patient survival with known prognostic factors for survival.

Results

The association of 53BP1 with several established prognostic factors was examined, including stage, tumor grade, surgical margin, peripancreatic extension, lymph node ratio (LNR), and CA 19–9. We found that 53BP1 modified the effects of known prognostic variables including LNR and CA 19–9 on survival outcomes. When 53BP1 intensity was low, increased LNR was associated with decreased OS (HR 4.84, 95% CI (2.26, 10.37), p<0.001) and high CA19-9 was associated with decreased OS (HR 1.72, 95% CI (1.18, 2.51), p=0.005). When 53BP1 intensity was high, LNR and CA19-9 were no longer associated with OS (p=0.958 and p=0.606, respectively).

Conclusions

In this study, 53BP1, a key player in DNA damage response and repair, was found to modify the prognostic value of two established prognostic factors, LNR and CA 19–9, suggesting 53BP1 may alter tumor behavior and ultimately impact how we interpret the value of other prognostic factors.

Keywords:
BRCA1 protein; 53BP1; Pancreatic cancer; DNA damage; Repair