Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
PLoS One. 2021 May 10;16(5):e0250986. doi: 10.1371/journal.pone.0250986. eCollection 2021.
Yes-associated protein 1 (YAP1) is a key effector molecule regulated by the Hippo pathway and described as a poor prognostic factor in breast cancer. Tumor protein 53 (TP53) mutation is well known as a biomarker related to poor survival outcomes. So far clinical characteristics and survival outcome according to YAP1 and TP53 mutation have been poorly identified in breast cancer.
Retrospectively, 533 breast tumor tissues were collected at the Seoul St Mary's hospital and Gangnam Severance Hospital from 1992 to 2017. Immunohistochemistry with YAP1 and p53 specific antibodies were performed, and the clinical data were analyzed.
Mutant p53 pattern was associated with aggressive tumor features and advanced anatomical stage. Inferior overall survival (OS) and recurrence free survival (RFS) were related with mutant p53 pattern cases with low nuclear YAP1 expression (P = 0.0009 and P = 0.0011, respectively). Multivariate analysis showed that mutant p53 pattern was an independent prognostic marker for OS [hazard ratios (HR): 2.938, 95% confidence intervals (CIs): 1.028-8.395, P = 0.044] and RFS (HR: 1.842, 95% CIs: 1.026-3.304). However, in cases with high nuclear YAP1 expression, there were no significantly difference in OS and RFS according to p53 staining pattern.
We found that mutant p53 pattern is a poor prognostic biomarker in breast tumor with low nuclear YAP1 expression. Our findings suggest that interaction between nuclear YAP1 and p53 expression pattern impact survival outcomes.
Yes 相关蛋白 1(YAP1)是 Hippo 通路调控的关键效应分子,被描述为乳腺癌的预后不良因素。肿瘤蛋白 53(TP53)突变是众所周知的与不良生存结局相关的生物标志物。迄今为止,乳腺癌中 YAP1 和 TP53 突变的临床特征和生存结局尚未得到充分确定。
回顾性地,从 1992 年至 2017 年,在首尔圣玛丽医院和江南塞弗伦斯医院收集了 533 例乳腺肿瘤组织。进行了 YAP1 和 p53 特异性抗体的免疫组织化学染色,并分析了临床数据。
突变型 p53 模式与侵袭性肿瘤特征和晚期解剖分期相关。总体生存(OS)和无复发生存(RFS)较差与低核 YAP1 表达的突变型 p53 模式病例相关(P=0.0009 和 P=0.0011)。多变量分析显示,突变型 p53 模式是 OS[风险比(HR):2.938,95%置信区间(CI):1.028-8.395,P=0.044]和 RFS(HR:1.842,95%CI:1.026-3.304)的独立预后标志物。然而,在核 YAP1 表达较高的情况下,p53 染色模式对 OS 和 RFS 无显著差异。
我们发现,在核 YAP1 表达较低的乳腺肿瘤中,突变型 p53 模式是预后不良的生物标志物。我们的研究结果表明,核 YAP1 与 p53 表达模式之间的相互作用影响生存结局。