Endometrial Tumor Classification by Histomorphology and Biomarkers in the Nurses' Health Study.
Endometrial Tumor Classification by Histomorphology and Biomarkers in the Nurses' Health Study.
复制标题
DOI：
10.1155/2021/8884364
复制
发表时间：
2021
影响因子：
1.8
通讯作者：
Mutter GL
中科院分区：
文献类型：
--
作者：
Watkins JC;Downing MJ;Crous-Bou M;Busch EL;Chen M;De Vivo I;Mutter GL
子宫内膜癌历来是根据组织形态学表现进行分类的，但观察者之间存在分歧。随着分子和生物标志物检测的日益普及，组织形态学诊断的预后意义和准确性受到质疑。为了解决这些问题的一个大的，前瞻性的队列研究，我们提供了一个集中的病理学审查和生物标志物分析的结果，所有偶发子宫内膜癌发生在1976年和2012年之间的护士健康研究。 对所有病例（n = 360）的常规组织学进行组织形态学诊断。随后将病例种植在组织微阵列中以探索各种生物标志物（例如，ER、PR、p53、PTEN、PAX2、AMACR、HNF 1 β、Napsin A、p16、PAX8和GATA 3）。 组织学类型包括类肉瘤（87.2%）、浆液性肉瘤（5.6%）、癌肉瘤（3.9%）、透明细胞型（1.7%）和混合型（1.7%）。组织学亚型内的生物标志物结果与现有文献一致：异常p53常见于浆液性病例（74%），HNF 1 β（67%）、Napsin A（67%）和AMACR（83%）表达常见于透明细胞癌。我们的数据集还允许检查非预选组织学中的生物标志物表达。结果表明：（1）HNF 1 β对透明细胞癌没有特异性，（2）TP53突变发生在许多组织学类型中，（3）GATA 3在多种组织型中表达，75%的阳性病例表现出高级别特征。 我们的研究结果确立了护士健康研究中发生的子宫内膜癌亚型，证实了某些已确立的生物标志物的敏感性，并对先前确定的某些生物标志物（例如，HNF1B）和特定组织型。
Endometrial cancers have historically been classified by histomorphologic appearance, which is subject to interobserver disagreement. As molecular and biomarker testing has become increasingly available, the prognostic significance and accuracy of histomorphologic diagnoses have been questioned. To address these issues for a large, prospective cohort study, we provide the results of a centralized pathology review and biomarker analysis of all incidental endometrial carcinomas occurring between 1976 and 2012 in the Nurses' Health Study. Routine histology of all (n = 360) cases was reviewed for histomorphologic diagnosis. Cases were subsequently planted in a tissue microarray to explore expression of a variety of biomarkers (e.g., ER, PR, p53, PTEN, PAX2, AMACR, HNF1β, Napsin A, p16, PAX8, and GATA3). Histologic subtypes included endometrioid (87.2%), serous (5.6%), carcinosarcoma (3.9%), clear cell (1.7%), and mixed type (1.7%). Biomarker results within histologic subtypes were consistent with existing literature: abnormal p53 was frequent in serous cases (74%), and HNF1β (67%), Napsin A (67%), and AMACR (83%) expression was frequent in clear cell carcinomas. Our dataset also allowed for examination of biomarker expression across non-preselected histologies. The results demonstrated that (1) HNF1β was not specific for clear cell carcinoma, (2) TP53 mutations occurred across many histologies, and (3) GATA3 was expressed across multiple histotypes, with 75% of positive cases demonstrating high-grade features. Our findings establish the subtypes of endometrial cancer occurring in the Nurses' Health Study, corroborate the sensitivity of certain well-established biomarkers, and call into question previously identified associations between certain biomarkers (e.g., HNF1B) and particular histotypes.