目的:乳腺癌(BC)中TP53突变与化疗耐药有关,内分泌治疗抵抗,和晚期复发,导致预后不良。免疫组织化学(IHC)中p53的核积累是TP53突变的替代标记。这项研究分析了频率,type,和TP53突变在BCs中的分布,并评估p53IHC作为TP53突变的替代标记的功效。
方法:我们收集了112例BC病例的数据,包括p53IHC和下一代测序(NGS)的结果。
结果:在36例患者中观察到p53IHC的过度表达(32.1%),19例患者完全缺失(17.0%),1例患者(0.9%)异常细胞质染色,56例(50.0%)患者为野生型。所有BCs中TP53突变与p53IHC的一致率为88.4%,腔内BCs占89.9%,三阴性BCs(TNBC)占86.0%。TNBC,异常p53IHC模式,p53IHC过表达,新辅助化疗(NAC)病史,TP53突变,高治疗前ki-67标记指数(≥50%)与更差的无远处转移生存率(DMFS)和总生存率(OS)显著相关(p<0.05)。NAC前临床III期与不良DMFS相关,但与OS无关。多因素分析显示,NAC病史,TNBC,p53IHC过表达是DMFS恶化的独立预测因子。异常的p53IHC模式和NAC病史是OS恶化的独立预测因子。
结论:P53IHC是BC中TP53突变的有效替代标记。异常p53的积累,无论TP53突变,与更差的DMFS相关,可以用作易于获得的生物标志物来预测化学耐药性。
OBJECTIVE: TP53 mutation in breast cancer (BC) is associated with chemoresistance, endocrine therapy resistance, and late recurrence, resulting in poor prognosis. Nuclear accumulation of p53 in immunohistochemistry (IHC) is a surrogate marker of TP53 mutation. This study analyzed the frequency, type, and distribution of TP53 mutations in BCs and assessed the efficacy of p53 IHC as a surrogate marker of TP53 mutation.
METHODS: We collected data from 112 BC cases, including the results of p53 IHC and next-generation sequencing (NGS).
RESULTS: Over-expression of p53 IHC was observed in 36 patients (32.1%), complete absence in 19 patients (17.0%), aberrant cytoplasmic staining in 1 patient (0.9%), and wild-type in 56 (50.0%) patients. The concordance rate between TP53 mutation and p53 IHC was 88.4% in all BCs, 89.9% in luminal BCs, and 86.0% in triple-negative BCs (TNBC). TNBC, abnormal p53 IHC pattern, p53 IHC over-expression, neoadjuvant chemotherapy (NAC) history, TP53 mutation, and high pre-treatment ki-67 labeling index (≥50%) were significantly associated with worse distant metastasis-free survival (DMFS) and overall survival (OS) (p<0.05). Pre-NAC clinical stage III was associated with worse DMFS but not OS. Multivariate analysis showed that NAC history, TNBC, and p53 IHC over-expression were independent predictors of worse DMFS. An abnormal p53 IHC pattern and NAC history were independent predictors of worse OS.
CONCLUSIONS: P53 IHC is a valid surrogate marker of TP53 mutation in BC. Accumulation of abnormal p53 alone, regardless of TP53 mutation, was associated with worse DMFS and can be used as an easily accessible biomarker to predict chemoresistance.