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

作者：Kim Ji Yeon; Park Kyunghee; Jung Hae Hyun; Lee Eunjin; 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^*

来源：Cancer Research and Treatment, 2016, 48(4): 1338-1350.

DOI：10.4143/crt.2015.430

• Tumor suppressor protein p53
• Triple-negative breast neoplasms
• Prognosis
• AmpliSeq
• nCounter mRNA expression assay
• Immunohistochemistry

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.

• 出版日期2016-10