Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are both associated with endometriosis but differ in histologic phenotype, biomarker profile, and survival. Our objectives were to refine immunohistochemical (IHC) panels that help distinguish the histotypes and reassess the prevalence of mismatch repair deficiency (MMRd) in immunohistochemically confirmed OCCC. We selected 8 candidate IHC markers to develop first-line and second-line panels in a training set of 344 OCCC/OEC cases. Interobserver reproducibility of histotype diagnosis was assessed in an independent testing cohort of 100 OCC/OEC initially without and subsequently with IHC. The prevalence of MMRd was evaluated using the testing cohort and an expansion set of 844 ovarian carcinomas. The 2 prototypical combinations (OCCC: Napsin A+/HNF1B diffusely+/PR-; OEC: Napsin A-/HNF1B nondiffuse/PR+) occurred in 75% of cases and were 100% specific. A second-line panel (ELAPOR1, AMACR, CDX2) predicted the remaining cases with 83% accuracy. Integration of IHC improved interobserver reproducibility (κ=0.778 vs. 0.882, P<0.0001). The prevalence of MMRd was highest in OEC (11.5%, 44/383), lower in OCCC (1.7%, 5/297), and high-grade serous carcinomas (0.7%, 5/699), and absent in mucinous (0/126) and low-grade serous carcinomas (0/50). All 5 MMRd OCCC were probable Lynch syndrome cases with prototypical IHC profile but ambiguous morphologic features: 3/5 with microcystic architecture and 2/5 with intratumoral stromal inflammation. Integration of first-line and second-line IHC panels increases diagnostic precision and enhances prognostication and triaging for predisposing/predictive molecular biomarker testing. Our data support universal Lynch syndrome screening in all patients with OEC when the diagnosis of other histotypes has been vigorously excluded.

中文翻译：

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准确区分卵巢透明细胞与子宫内膜样癌需要整合表型、免疫组织化学预测和基因型：对林奇综合征筛查的影响。

卵巢透明细胞癌 (OCCC) 和卵巢子宫内膜样癌 (OEC) 均与子宫内膜异位症相关，但在组织学表型、生物标志物谱和生存方面有所不同。我们的目标是完善免疫组织化学 (IHC) 组合，帮助区分组织型并重新评估免疫组织化学证实的 OCCC 中错配修复缺陷 (MMRd) 的患病率。我们选择了 8 个候选 IHC 标记物，在 344 个 OCCC/OEC 病例的训练集中开发一线和二线组。在由 100 名 OCC/OEC 组成的独立测试队列中评估组织型诊断的观察者间再现性，最初不使用 IHC，随后使用 IHC。使用测试队列和 844 例卵巢癌的扩展组来评估 MMRd 的患病率。2 种典型组合（OCCC：Napsin A+/HNF1B 弥漫性+/PR-；OEC：Napsin A-/HNF1B 非弥漫性/PR+）出现在 75% 的病例中，并且具有 100% 的特异性。二线小组（ELAPOR1、AMACR、CDX2）以 83% 的准确率预测其余病例。IHC 的整合提高了观察者间的重现性（κ=0.778 与 0.882，P<0.0001）。MMRd 在 OEC 中的患病率最高（11.5%，44/383），在 OCCC 中较低（1.7%，5/297）和高级别浆液性癌（0.7%，5/699），在粘液性癌中不存在（0 /126) 和低度浆液性癌 (0/50)。所有 5 例 MMRd OCCC 均为可能的 Lynch 综合征病例，具有典型的 IHC 特征，但形态学特征不明确：3/5 具有微囊结构，2/5 具有瘤内间质炎症。一线和二线 IHC 组合的集成提高了诊断精度，并增强了易感性/预测性分子生物标志物测试的预测和分类。我们的数据支持在大力排除其他组织型诊断的情况下对所有 OEC 患者进行普遍的林奇综合征筛查。