小痣而非鳞状分化是子宫内膜癌和癌前病变中CTNNB1 (β-catenin)突变的可靠指标。

Shuang Niu, Elena Lucas, Kyle Molberg, Amanda Strickland, Yan Wang, Kelley Carrick, Glorimar Rivera-Colon, Katja Gwin, Jeffrey A SoRelle, Diego H Castrillon, Wenxin Zheng, Hao Chen
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引用次数: 6

摘要

虽然在子宫内膜样癌(EEC)和不典型增生/子宫内膜样上皮内瘤变(AH/EIN)中统称为“鳞状分化(SD)”,但小痣(通常称为“鳞状小痣”)和真SD可能代表两种不同的现象。在这里,我们探讨了小粒与SD之间的区别,并研究了小粒和SD与CTNNB1突变的关系。共研究270例EEC和AH/EIN,其中EEC有(n=36)个或无(n=36)个病灶,AH/EIN有(n=80)个或无(n=118)个病灶。采用免疫组织化学方法对病例进行分析,选择20例采用靶向新一代测序技术。AH/EIN和EEC的小分子和腺β-连环蛋白核染色几乎完全一致。在AH/EIN中,小分子与腺β-连环蛋白核染色呈正相关(P <0.0001, Φ=0.59;P <0.0001, Φ=0.85 (EEC)。(2) SD与β-catenin、PAX2或PTEN的异常表达无关(Φ=0.09, β-catenin;Φ= 0.16,我们;Φ= 0.13,PTEN)。在所有20例选定的含摩尔病例(100%)中均鉴定出CTNNB1突变。对来自1名患者的2个(黄体酮治疗前和黄体酮治疗后)活检进行了新一代测序,揭示了相同的痣和腺体突变谱。综上所述,(1)SD和morules是不同的生物现象;(2)在EEC和AH/EIN中存在morules而不是SD是CTNNB1突变的可靠指标。我们的研究结果表明SD和morules是不同的生物学现象。由于小痣与β-连环蛋白突变相关,而SD与β-连环蛋白突变无关,因此这种区别具有临床相关性,应纳入诊断报告。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (β-catenin) Mutations in Endometrial Carcinoma and Precancers.

Although collectively regarded as "squamous differentiation (SD)" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as "squamous morules") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n=36) or without (n=36) morules and AH/EIN with (n=80) or without (n=118) morules. Cases were analyzed by immunohistochemistry and selected cases (n=20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular β-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular β-catenin nuclear staining ( P <0.0001, Φ=0.59 in AH/EIN; P <0.0001, Φ=0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of β-catenin, PAX2 or PTEN (Φ=0.09, β-catenin; Φ=0.16, PAX2; Φ=0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with β-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.

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