Department of Pathology, Turku University Hospital, University of Turku, Turku, Finland.
Department of Molecular Oncology, University of British Columbia, Vancouver, BC, Canada.
Histopathology. 2023 Dec;83(6):880-890. doi: 10.1111/his.15029. Epub 2023 Aug 14.
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.
p53 亚克隆表达（野生型到突变型染色的突然转变）的意义尚未得到充分理解，子宫内膜癌（EC）的 NSMP 和 p53abn 分子亚型之间的 10%任意诊断截止值尚未得到严格评估。我们的目的是描述 EC 中 p53 亚克隆和差异表达/TP53 测序结果，并评估其临床意义。
记录了 957 例 EC 全切片的 p53 亚克隆免疫组化。评估了 TP53 突变评估与 p53 免疫组化之间的一致性。在 957 例病例中，有 4.0%（38 例）出现 p53 亚克隆 IHC 染色，其中 957 例中有 23 例（2.4%）在≥10%的肿瘤细胞中出现突变型 p53 染色。它最常见于 POLEmut（65 例中的 9 例，14%）和 MMRd（274 例中的 13 例，4.7%）EC（“多分类器”EC），其中 p53 亚克隆染色不影响分子亚型诊断。排除 POLEmut 和 MMRd EC 后，有 11 例（1.1%）≥10%的 p53 亚克隆，其中 4 例患者死于疾病，而在 5 例 p53 突变型染色<10%的患者中，没有因疾病导致的死亡。p53 免疫组化与 TP53 测序之间的一致性为 92.6%；大多数不一致的结果发生在超突变 POLEmut 或高度突变 MMRd EC 中。在 NSMP 和 p53abn EC 中，IHC 和测序之间的一致性为 95.8%。
排除“多分类器”EC 后，仅在 1.1%的 EC 中存在 p53 亚克隆染色≥10%。≥10%的 p53 亚克隆染色的截止值确定了死于 EC 的风险增加的患者，支持其用于诊断 p53abn 分子亚型。
