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Cancer Res Treat. 2016 Oct;48(4):1338-1350. Epub 2016 Feb 18.

Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer.

Author information

1
Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Samsung Genome Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
3
Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Cancer of Companion Diagnostics, Innovative Cancer Medicine Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Life Science Solutions Group, Thermo Fisher Scientific Corporation, Seoul, Korea.
6
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

PURPOSE:

TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).

MATERIALS AND METHODS:

We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients.

RESULTS:

Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with a TP53 missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).

CONCLUSION:

Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.

KEYWORDS:

AmpliSeq; Immunohistochemistry; Prognosis; Triple-negative breast neoplasms; Tumor Suppressor Protein p53; nCounter mRNA expression assay

PMID:
26910472
PMCID:
PMC5080805
DOI:
10.4143/crt.2015.430
[Indexed for MEDLINE]
Free PMC Article

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