Institute of Pathology, Friedrich Alexander Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Germany,
Virchows Arch. 2014 Jun;464(6):663-72. doi: 10.1007/s00428-014-1569-7. Epub 2014 Apr 12.
Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.
用于诊断锯齿状结直肠病变（增生性息肉、无或有异型增生的无蒂锯齿状腺瘤——我们称之为混合息肉——和传统锯齿状腺瘤）的标准已经达成共识，应在观察者间的可重复性方面验证其在日常实践中的适用性，并验证其与临床特征和（表）遗传事件的相关性。通过选择所有无蒂锯齿状腺瘤、传统锯齿状腺瘤和混合息肉，从一系列连续的结直肠息肉（n=1926）中创建了一个研究集。我们添加了连续的增生性息肉、经典腺瘤和正常黏膜样本，总共 200 个样本。通过这个系列，我们进行了一项观察者间研究，涵盖了来自五个欧洲国家的具有胃肠道病理学经验的十位病理学家，共进行了三轮，所有病例均进行了显微镜评估。评估了单个形态学标准，并将这些标准与临床参数以及 KRAS、BRAF 和 PIK3CA 的突变状态和 MLH1 的甲基化状态相关联。性别、年龄和部位与某些类型的病变显著相关。Kappa 统计显示，息肉分类的观察者间一致性为中等至良好（κ=0.56 至 0.63），但对于单个标准，差异很大（κ=0.06 至 0.82）。BRAF 突变在增生性息肉（86%，62/72）和无蒂锯齿状腺瘤（80%，41/51）中经常发生。KRAS 突变在传统锯齿状腺瘤（78%，7/9）中更常见，而在经典腺瘤（20%，10/51）中则不常见。无蒂锯齿状腺瘤的单个形态学标准与 BRAF 突变显著相关（所有 p 值均≤0.001），而经典腺瘤或传统锯齿状腺瘤的标准与 KRAS 突变显著相关（所有 p 值均<0.001）。因此，单个明确的形态学标准可预测结直肠息肉中的遗传改变。
