Emerging therapies for non-small cell lung cancer targeting c-Met overexpression have recently demonstrated promising results. However, the evaluation of c-Met expression can be challenging. We aimed to study the inter and intraobserver reproducibility of c-Met expression evaluation. One hundred ten cases with non-small cell lung cancer (40 biopsies and 70 surgical specimens) were retrospectively selected in a single laboratory (LPCE) and evaluated for c-Met expression. Six pathologists (4 seniors and 2 juniors) evaluated the H-score and made a 3-tier classification of c-Met expression for all cases, using conventional light microscopy (CLM) and whole slide imaging (WSI). The interobserver reproducibility with CLM gave global Cohen Kappa coefficients (ƙ) ranging from 0.581 (95% CI: 0.364-0.771) to 0.763 (95% CI: 0.58-0.92) using the c-Met 3-tier classification and H-score, respectively. ƙ was higher for senior pathologists and biopsy samples. The interobserver reproducibility with WSI gave a global ƙ ranging from 0.543 (95% CI: 0.33-0.724) to 0.905 (95% CI: 0.618-1) using the c-Met H-score and 2-tier classification (≥25% 3+), respectively. ƙ for intraobserver reproducibility between CLM and WSI ranged from 0.713 to 0.898 for the c-Met H-score and from 0.600 to 0.779 for the c-Met 3-tier classification. We demonstrated a moderate to excellent interobserver agreement for c-Met expression with a substantial to excellent intraobserver agreement between CLM and WSI, thereby supporting the development of digital pathology. However, some factors (scoring method, type of tissue samples, and expertise level) affect reproducibility. Our findings highlight the importance of establishing a consensus definition and providing further training, particularly for inexperienced pathologists, for c-Met immunohistochemistry assessment in clinical practice.

中文翻译：

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使用传统光学显微镜和全玻片成像对非小细胞肺癌进行 c-Met 免疫组织化学评分（克隆 SP44）的重现性。


针对 c-Met 过度表达的非小细胞肺癌新兴疗法最近显示出有希望的结果。然而，c-Met 表达的评估可能具有挑战性。我们的目的是研究 c-Met 表达评估的观察者间和观察者内再现性。在单一实验室 (LPCE) 中回顾性选择 110 例非小细胞肺癌病例（40 个活检样本和 70 个手术样本）并评估 c-Met 表达。六名病理学家（4 名高级人员和 2 名初级人员）使用传统光学显微镜 (CLM) 和全玻片成像 (WSI) 评估了 H 评分，并对所有病例的 c-Met 表达进行了 3 级分类。使用 c-Met 3 层分类和 H 分数，CLM 的观察者间重现性给出的全局 Cohen Kappa 系数 (ƙ) 范围为 0.581（95% CI：0.364-0.771）至 0.763（95% CI：0.58-0.92），分别。 ƙ 对于高级病理学家和活检样本而言较高。使用 c-Met H 分数和 2 级分类（≥25% 3），WSI 的观察者间重现性给出的全局 ƙ 范围为 0.543（95% CI：0.33-0.724）至 0.905（95% CI：0.618-1） +) 分别。 ƙ 对于 CLM 和 WSI 之间的观察者内重现性，c-Met H 分数的范围为 0.713 至 0.898，c-Met 3 层分类的范围为 0.600 至 0.779。我们展示了 c-Met 表达的中等至优秀的观察者间一致性，以及 CLM 和 WSI 之间的显着至优秀的观察者内一致性，从而支持了数字病理学的发展。然而，一些因素（评分方法、组织样本类型和专业水平）会影响重现性。 我们的研究结果强调了在临床实践中对 c-Met 免疫组织化学评估建立共识定义和提供进一步培训的重要性，特别是对于缺乏经验的病理学家。