The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually—and more importantly as a group—has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.

在某些情况下，子宫内膜不典型增生/子宫内膜样上皮内瘤变（AH/EIN）的诊断仍然具有挑战性和主观性，组织学标准各不相同，妇科病理学家之间的意见也存在差异，可能导致治疗不足/过度。人们对使用特异性免疫组织化学标记物作为 AH/EIN 诊断的辅助手段越来越感兴趣。例如，世界卫生组织 2020 年分类指定 Pten、Pax2 或错配修复蛋白的丢失是理想的诊断标准。其他标记物，尤其是 β-catenin 和 Arid1a，也在一些 AH/EIN 中异常表达。然而，一些标记物的单独性能（更重要的是作为一组标记物）尚未经过严格的探索，这引发了关于哪种标记物或组合在实践中最有效的问题。通过免疫组织化学分析 AH/EIN 病例 (n=111) 的福尔马林固定石蜡包埋的组织切片中的6 种标记物：Pax2、Pten、Mlh1、β-连环蛋白、Arid1a 和 p53。将每个病例和标记的异常表达制成表格。还分析了另一组正常子宫内膜 (n=79)，以确定标记物异常的最佳诊断标准。对每个标记、整个组及其子集的性能特征进行定量和统计分析。按照检测到的病例数量顺序，AH/EIN 中最常见的异常标记物是 Pax2（81.1% 病例）、Pten（50.5%）、β-连环蛋白（47.7%）、Arid1a（7.2%）、Mlh1（4.5%） ）和 p53（2.7%）。大多数病例显示≥2个标记物的异常表达。所有 6 个标记一起识别了 92.8% 的病例。Arid1a、Mlh1 和 p53 是稳健且易于评分的标记物，但所有显示这 3 个标记物异常表达的病例也可通过 Pax2、Pten 或 β-catenin 检测到。仅由 3 个标记物（Pax2、Pten 和 β-catenin）组成的集中组显示出作为 AH/EIN 组织病理学诊断辅助的最佳性能特征。该组合的使用切实可行且稳健，92.8% 的 AH/EIN 中 3 个标记中至少有 1 个存在异常。