Lee Miseon, Park In Ah, Heo Sun-Hee, Kim Young-Ae, Gong Gyungyub, Lee Hee Jin
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Pathol Transl Med. 2019 May;53(3):180-187. doi: 10.4132/jptm.2019.02.08. Epub 2019 Mar 11.
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.
大多数三阴性乳腺癌（TNBC）具有高组织学分级，与内质网应激水平升高相关，且TP53突变频率较高。TP53错义突变导致突变型p53蛋白的产生，通常表现为p53蛋白高表达。肿瘤浸润淋巴细胞（TILs）作为抗肿瘤免疫反应的一部分而积聚，在TNBC中具有很强的预后和预测意义。我们旨在阐明TNBC中p53表达与TILs数量之间的关联。
在678例TNBC患者中，我们评估了TILs水平和内质网应激分子的表达。p53蛋白表达的免疫组化检查分为三组：无表达、低表达和高表达。
分别在44.1%（n = 299）、20.1%（n = 136）和35.8%（n = 243）的患者中发现了p53无表达、低表达和高表达。与p53低表达的患者相比，p53高表达的患者表现出高组织学分级（p <.001）、高TILs水平（p =.009）和内质网应激相关分子的高表达（p-eIF2a，p =.013；XBP1，p =.007）。三个p53表达组之间的无病生存率（p =.406）或总生存率（p =.444）没有显著差异。
p53高表达与内质网应激分子表达增加和TILs浸润增加相关。
