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KMID : 0939920160480041338
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대한암학회지
2016 Volume.48 No. 4 p.1338 ~ p.1350
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Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer
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Kim Ji-Yeon
Park Kyung-Hee
Jung Hae-Hyun
Lee Eun-Jin
Cho Eun-Yoon
Lee Kwang-Hee
Bae Soo-Youn
Lee Se-Kyung
Kim Seok-Won
Lee Jeong-Eon
Nam Seok-Jin
Ahn Jin-Seok
Im Young-Hyuck
Park Yeon-Hee
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Abstract
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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.
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KEYWORD
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Tumor Suppressor Protein p53, Triple-negative breast neoplasms, Prognosis, AmpliSeq, nCounter mRNA expression assay, Immunohistochemistry
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