Cancer Res Treat.  2016 Oct;48(4):1338-1350. 10.4143/crt.2015.430.

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

• Kim JY
• Park K
• Jung HH
• Lee E
• Cho EY
• Lee KH
• Bae SY
• Lee SK
• Kim SW
• Lee JE
• Nam SJ
• Ahn JS
• Im YH
• Park YH

• KMID: 2356236
• DOI: http://doi.org/10.4143/crt.2015.430

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.

Keyword

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

MeSH Terms

Breast Neoplasms
Humans
Immunohistochemistry
Mutation, Missense
Prognosis
RNA, Messenger
Sequence Analysis, DNA
Sequence Deletion
Triple Negative Breast Neoplasms*
Tumor Suppressor Protein p53
RNA, Messenger
Tumor Suppressor Protein p53

Figure

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  Fig. 1. Significant TP53 mutant genes and clinical features.

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  Fig. 2. Correlation between TP53 mutation status and mRNA expression (A), correlation between TP53 mutation status and protein expression (B), and correlation between TP53 mRNA and p53 protein expression (C). IHC, immunohistochemisty.

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  Fig. 3. Kaplan-Meier curve for distant recurrence-free survival according to TP53 mutation status (wide type [WT]) (A), p53 protein expression by immunohistochemistry (IHC) (B), TP53 expression by nCounter expression assay (C), and mutation and expression status by nCounter expression assay (D). MM, missense mutation; SM, mutation causing gene silencing.

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  Fig. 4. Kaplan-Meier curve for distant recurrence-free survival according to expression status by nCounter expression assay in TP53 wild type (WT) (A), missense TP53 mutation (MM) (B), and TP53 mutation causing gene silencing (SM) (C).

Reference

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