Abstract

BackgroundTP53 status based on TP53 signature, a gene expression profile to determine the presence or absence of TP53 mutation, is an independent prognostic factor of breast cancer. The purpose of this study was to develop a simple diagnostic system for TP53 signature status.MethodsWe developed a multiplex reverse transcription–polymerase chain reaction system to determine TP53 status. Based on this system, prospectively collected 189 patients with stage I and II breast cancer were determined to have TP53 mutant signature or TP53 wild-type signature. The prognostic significance of the TP53 signature by the diagnostic system was analyzed.ResultsThe diagnostic accuracy of TP53 status and reproducibility of this diagnosis system was confirmed. Using the diagnostic system, 89 patients were classified as TP53 mutant signature and the remaining 100 cases were classified as TP53 wild-type signature. Recurrence-free survival (RFS) among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature. On univariate and multivariate analyses, the TP53 signature status was an independent predictor of RFS. RFS among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature in a cohort of estrogen receptor-positive breast cancer. Although a difference was not significant, no recurrent cases was observed in TP53 wild-type signature group in triple negative breast cancer.ConclusionThis simple and precise diagnostic system to determine TP53 signature status may help in prognostic assessment, therapeutic decision-making, and treatment optimization in patients with breast cancer.

Highlights

  • The plethora of comprehensive gene expression analyses in the context of breast cancer has gradually helped unravel the molecular biology of breast cancer

  • Our results indicate that TP53 signature based on multiplex reverse transcription–polymerase chain reaction (RT–PCR) was an independent predictor of Recurrence-free survival (RFS)

  • The TP53 mutation has long been known as an independent predictor of poor prognosis among patients with breast cancer [10, 11]

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Summary

Introduction

The plethora of comprehensive gene expression analyses in the context of breast cancer has gradually helped unravel the molecular biology of breast cancer. TP53 status based on TP53 signature, a gene expression profile to determine the presence or absence of TP53 mutation, is an independent prognostic factor of breast cancer. Methods We developed a multiplex reverse transcription–polymerase chain reaction system to determine TP53 status Based on this system, prospectively collected 189 patients with stage I and II breast cancer were determined to have TP53 mutant signature or TP53 wild-type signature. Recurrence-free survival (RFS) among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature. RFS among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature in a cohort of estrogen receptor-positive breast cancer. Conclusion This simple and precise diagnostic system to determine TP53 signature status may help in prognostic assessment, therapeutic decision-making, and treatment optimization in patients with breast cancer

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