Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Digital Health, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Anticancer Res. 2024 Sep;44(9):3983-3994. doi: 10.21873/anticanres.17227.
BACKGROUND/AIM: 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.
We collected data from 112 BC cases, including the results of p53 IHC and next-generation sequencing (NGS).
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.
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.
背景/目的：乳腺癌（BC）中 TP53 突变与化疗耐药、内分泌治疗耐药和晚期复发有关，导致预后不良。免疫组化（IHC）中 p53 的核积累是 TP53 突变的替代标志物。本研究分析了 BC 中 TP53 突变的频率、类型和分布，并评估了 p53 IHC 作为 TP53 突变替代标志物的疗效。
我们收集了 112 例 BC 病例的数据，包括 p53 IHC 和下一代测序（NGS）的结果。
在 36 例患者（32.1%）中观察到 p53 IHC 过表达，在 19 例患者（17.0%）中完全缺失，在 1 例患者（0.9%）中出现异常细胞质染色，在 56 例患者（50.0%）中为野生型。所有 BC 中 TP53 突变与 p53 IHC 的一致性率为 88.4%，在 luminal BC 中为 89.9%，在三阴性 BC（TNBC）中为 86.0%。TNBC、异常 p53 IHC 模式、p53 IHC 过表达、新辅助化疗（NAC）史、TP53 突变和高治疗前 ki-67 标记指数（≥50%）与远处无转移生存率（DMFS）和总生存率（OS）较差显著相关（p<0.05）。NAC 前临床 III 期与较差的 DMFS 相关，但与 OS 无关。多变量分析显示，NAC 史、TNBC 和 p53 IHC 过表达是 DMFS 较差的独立预测因素。异常 p53 IHC 模式和 NAC 史是 OS 较差的独立预测因素。
p53 IHC 是 BC 中 TP53 突变的有效替代标志物。单独异常 p53 的积累，无论是否存在 TP53 突变，均与较差的 DMFS 相关，可作为一种易于获得的生物标志物，用于预测化疗耐药性。
