Introduction: Overexpression of the mesenchymal-epithelial transition (MET) receptor, a receptor tyrosine kinase, can propel the growth of cancer cells and portends poor prognoses for patients with lung cancer. Evaluation of MET by immunohistochemistry is challenging, with MET protein overexpression varying from 20% to 80% between lung cancer cohorts. Clinical trials using MET protein expression to select patients have also reported a wide range of positivity rates and outcomes. Materials and Methods: To overcome this variability, the Lung Cancer Mutation Consortium Pathologist Panel endeavored to standardize the evaluation of MET protein expression with “Round Robin” conferences. This panel used randomly selected Aperio-scanned formalin-fixed paraffin-embedded lung cancer specimens stained by MET immunohistochemistry for the Lung Cancer Mutation Consortium 2.0 study (N=838). Seven pathologists in separate laboratories scored images of 5 initial cases and 2 subsequent rounds of 39 cases. The pathologists’ scores were compared for consistency using the intraclass correlation coefficient. Issues affecting reproducibility were discussed in Round Robin conferences between rounds, and steps were taken to improve scoring consistency, such as sharing reference materials and example images. Results: The overall group intraclass correlation coefficient comparing the consistency of scoring improved from 0.50 (95% confidence interval, 0.37-0.64) for the first scoring round to 0.74 (95% confidence interval, 0.64-0.83) for the second round. Discussion: We found that the consistency of MET immunohistochemistry scoring is improved by continuous training and communication between pathologists.

中文翻译：

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肺腺癌中 MET 蛋白表达的循环评估提高了观察者间的一致性

简介：间充质-上皮转化 (MET) 受体（一种受体酪氨酸激酶）的过度表达可促进癌细胞的生长，并预示肺癌患者的预后不良。通过免疫组织化学评估 MET 具有挑战性，MET 蛋白过表达在肺癌队列之间从 20% 到 80% 不等。使用 MET 蛋白表达来选择患者的临床试验也报告了广泛的阳性率和结果。材料和方法：为了克服这种可变性，肺癌突变联盟病理学家小组努力通过“循环”会议对 MET 蛋白表达的评估进行标准化。该小组使用随机选择的经 MET 免疫组织化学染色的 Aperio 扫描福尔马林固定石蜡包埋肺癌样本用于肺癌突变联盟 2.0 研究 (N=838)。不同实验室的七名病理学家对 5 个初始病例和随后的 2 轮 39 个病例的图像进行了评分。使用组内相关系数比较病理学家评分的一致性。轮次之间的循环会议讨论了影响再现性的问题，并采取了一些措施来提高评分的一致性，例如共享参考资料和示例图像。结果：比较评分一致性的总体组内相关系数从第一轮评分的 0.50（95% 置信区间，0.37-0.64）提高到 0.74（95% 置信区间，0.64-0. 83) 第二轮。讨论：我们发现 MET 免疫组化评分的一致性通过病理学家之间的持续培训和交流得到改善。