对于p53的亚克隆表达（从野生型过渡到突变类型染色的突变模式），其意义尚不明确，而在子宫内膜癌（EC）的NSMP和p53abn分子亚型之间的10％诊断截断值并未经过重要评估。我们的目标是表征EC中亚克隆p53的情况和p53表达/TP53测序结果的不一致，并评估它们的临床意义。记录了来自957个EC的全切片的亚克隆p53免疫染色。评估了TP53突变评估和p53免疫染色之间的一致性。957例中，4.0％（38例）显示亚克隆p53免疫染色，其中23例（2.4％）显示≥10％肿瘤细胞中的突变模式p53染色。它最常见于POLEmut（65例中9例，14％）和MMRd（274例中13例，4.7％）的EC（'多分类器' ECs），在这些情况下，亚克隆p53染色不会影响分子亚型诊断。在排除POLEmut和MMRd EC之后，957例中有11例（1.1％）显示出≥10％的亚克隆p53，其中四名患者因疾病死亡，而在少于10％突变模式p53染色的五名患者中没有疾病相关死亡。p53免疫染色和TP53测序之间的一致性为92.6％。大部分不一致的结果出现在超突变的POLEmut或高突变的MMRd EC中。在NSMP和p53abn EC之间，IHC和测序的一致性为95.8％。在排除了'多分类器' ECs后，仅有1.1％的EC显示≥10％的亚克隆p53染色。≥10％亚克隆p53染色的截断值可用于诊断p53abn分子亚型，以识别病情恶化风险增加的患者。© 2023 The Authors. 由John Wiley＆Sons Ltd.出版的《组织病理学》发表

The significance of subclonal expression of p53 (abrupt transition from wild-type to mutant-pattern staining) is not well understood, and the arbitrary diagnostic cut-off of 10% between NSMP and p53abn molecular subtypes of endometrial carcinoma (EC) has not been critically assessed. Our aim was to characterise subclonal p53 and discrepant p53 expression/TP53 sequencing results in EC and assess their clinical significance.Subclonal p53 immuostaining on whole sections from 957 ECs was recorded. Agreement between TP53 mutational assessment and p53 immunostaining was evaluated. Subclonal p53 IHC staining was seen in 4.0% (38 of 957) of cases, with 23 of 957 (2.4%) showing mutant-pattern p53 staining in ≥10% of tumour cells. It was most commonly seen in POLEmut (nine of 65, 14%) and MMRd (13 of 274, 4.7%) EC ('multiple classifier' ECs), where subclonal p53 staining does not impact the molecular subtype diagnosis. Excluding POLEmut and MMRd EC, 11 of 957 (1.1%) showed ≥10% subclonal p53 from which four patients died of disease, while there were no deaths due to disease in the five patients with <10% mutant-pattern p53 staining. Agreement between p53 immunostaining and TP53 sequencing was 92.6%; most of the discrepant results were in the ultramutated POLEmut or hypermutated MMRd ECs. In NSMP and p53abn EC the agreement between IHC and sequencing was 95.8%.Subclonal p53 staining ≥10% is present in only 1.1% of EC after excluding 'multiple classifier' ECs. The cut-off of ≥10% subclonal p53 staining identified patients at increased risk of dying from EC, supporting its use to diagnose p53abn molecular subtype.© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.