Niu Shuang, Molberg Kyle, Chen Jackson, Conrad Lesley, Lucas Elena, Chen Hao
Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pathology, Parkland Hospital, Dallas, TX 75235, USA.
Cancers (Basel). 2025 Apr 29;17(9):1495. doi: 10.3390/cancers17091495.
: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. : In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium ( = 57) and secretory phase endometrium ( = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. : The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. : Combined with previous research highlighting its effectiveness in other challenging contexts-such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN-this study provides strong evidence supporting the panel's broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN.
尽管治疗方案有所进步，但子宫内膜癌仍然对女性构成重大威胁，这凸显了早期检测非典型增生/子宫内膜样上皮内瘤变（AH/EIN）的重要性，AH/EIN是被广泛认可的子宫内膜癌组织学前驱病变。即便诊断AH/EIN的形态学标准有所完善，但对病理学家而言，准确诊断仍具挑战性，尤其是在存在分泌性改变的病例中。分泌相关变化导致的形态学改变使诊断标准的应用更加复杂，这凸显了对可靠生物标志物的需求。既往研究表明，由三种免疫组化标志物PAX2、PTEN和β-连环蛋白组成的检测组合可有效用于在各种非分泌情况下识别AH/EIN。在本研究中，使用该检测组合对分泌期子宫内膜中的69例AH/EIN进行了分析。还分析了良性增殖期子宫内膜（n = 57）和分泌期子宫内膜（n = 71）中PAX2、PTEN和β-连环蛋白的表达作为对照。该三标志物检测组合成功识别了93%的分泌性AH/EIN，与其在识别非分泌性真性AH/EIN（92.8%）和子宫内膜息肉内的AH/EIN（92.4%）中的表现相当。值得注意的是，良性增殖期子宫内膜中β-连环蛋白的表达通常显示为弱核染色（67%），在使用该三标志物检测组合时可能会造成诊断陷阱。总体而言，结果证明了该三标志物检测组合在临床实践中对识别具有挑战性的分泌期子宫内膜病例中的AH/EIN的诊断效用。结合先前强调其在其他具有挑战性的情况下（如息肉中的AH/EIN、小尺寸EIN（亚诊断性EIN）和孕激素治疗的EIN）有效性的研究，本研究提供了有力证据支持该检测组合在解决与AH/EIN精确诊断相关的主要诊断挑战方面的广泛适用性。
