Int J Gynecol Pathol. 2023 Sep 1;42(5):435-442. doi: 10.1097/PGP.0000000000000923. Epub 2022 Oct 11.
The interobserver reproducibility is poor for histotyping within the p53-abnormal molecular category of endometrial carcinomas (ECs); therefore, biomarkers that improve histologic classification are useful. β-catenin has been proposed to have prognostic significance in specific clinicopathologic and molecular contexts. The diagnostic utility for β-catenin expression patterns in determining the histotype of p53-abnormal ECs has not been well studied. We identified ECs molecularly classified as "p53-abnormal." The p53-abnormal classification was assigned when (1) no POLE exonuclease domain hotspot mutations identified, (2) mismatch-repair protein expression was retained, and (3) abnormal p53 expression (null or overexpression) was present. Morphology was re-reviewed and β-catenin immunohistochemistry was scored as abnormal (nuclear) or normal (membranous, non-nuclear). Eighty ECs were identified in the "p53-abnormal" category; 27 (33.75%) were uterine serous carcinomas, and 53 were of nonserous histotype: 28 uterine carcinosarcomas (35%), 16 endometrioid carcinomas (20%), 2 clear cell carcinomas (2.5%), and 7 high-grade EC with ambiguous morphology (8.75%). All 27 uterine serous carcinomas demonstrated membranous β-catenin staining. Of the 53 nonserous ECs, 11 (21%) showed abnormal β-catenin expression: 6 endometrioid carcinomas, 4 uterine carcinosarcoma, and 1 high-grade EC with ambiguous morphology. The specificity of abnormal β-catenin expression for nonserous EC is high (100%) but the sensitivity is low (21%) with positive and negative predictive values of 100% and 60%, respectively. Our data shows that abnormal β-catenin expression in the context of p53-abnormal EC is highly specific, but not sensitive, for nonserous ECs and may be of value as part of a panel in classifying high-grade EC, particularly to exclude uterine serous carcinoma when nuclear staining is present.
p53 异常分子分类内的子宫内膜癌（EC）组织学类型的观察者间可重复性较差；因此，改善组织学分类的生物标志物是有用的。β-连环蛋白在特定的临床病理和分子背景下具有预后意义。β-连环蛋白表达模式在确定 p53 异常 EC 组织类型中的诊断效用尚未得到很好的研究。我们鉴定了分子上被分类为“p53 异常”的 EC。当（1）未鉴定出 POLE 外切酶结构域热点突变，（2）错配修复蛋白表达保留，和（3）存在异常 p53 表达（缺失或过表达）时，将 p53 异常分类。对形态学进行重新审查，并对β-连环蛋白免疫组化进行评分，结果为异常（核）或正常（膜性，非核）。在“p53 异常”类别中鉴定出 80 例 EC；27 例（33.75%）为子宫浆液性癌，53 例为非浆液性组织类型：28 例子宫癌肉瘤（35%）、16 例子宫内膜样癌（20%）、2 例透明细胞癌（2.5%）和 7 例高级别伴有形态学不明确的 EC（8.75%）。所有 27 例子宫浆液性癌均显示膜性β-连环蛋白染色。在 53 例非浆液性 EC 中，有 11 例（21%）显示异常β-连环蛋白表达：6 例子宫内膜样癌、4 例子宫癌肉瘤和 1 例高级别伴有形态学不明确的 EC。异常β-连环蛋白表达对非浆液性 EC 的特异性很高（100%），但敏感性较低（21%），阳性预测值和阴性预测值分别为 100%和 60%。我们的数据表明，在 p53 异常 EC 背景下，异常β-连环蛋白表达对非浆液性 EC 高度特异，但不敏感，可能作为高级别 EC 分类的面板之一有价值，特别是在存在核染色时可排除子宫浆液性癌。
