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Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer.
- Source :
-
Cancer research and treatment [Cancer Res Treat] 2016 Oct; Vol. 48 (4), pp. 1338-1350. Date of Electronic Publication: 2016 Feb 18. - Publication Year :
- 2016
-
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).<br />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.<br />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).<br />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.<br />Competing Interests: relevant to this article was not reported.
- Subjects :
- Adult
Aged
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation, Missense genetics
Neoplasm Staging
RNA, Messenger genetics
Sequence Deletion genetics
Triple Negative Breast Neoplasms pathology
Biomarkers, Tumor genetics
Prognosis
Triple Negative Breast Neoplasms genetics
Tumor Suppressor Protein p53 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2005-9256
- Volume :
- 48
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 26910472
- Full Text :
- https://doi.org/10.4143/crt.2015.430