Kim Jung Ho, Kim Kyung-Ju, Bae Jeong Mo, Rhee Ye-Young, Cho Nam-Yun, Lee Hye Seung, Kang Gyeong Hoon
Department of Pathology, SMG-SNU Boramae Medical Centre, Seoul, Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
J Clin Pathol. 2015 Jan;68(1):22-8. doi: 10.1136/jclinpath-2014-202603. Epub 2014 Oct 16.
Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) is associated with a favourable prognosis and microsatellite instability-high (MSI-H) status. However, there is a lack of consensus on optimal criteria for CLR assessment. The aim of this study was to comparatively validate traditional and novel assessment criteria for CLR.
CLR status in 212 MSI-H CRCs was assessed independently by two pathologists using three different criteria: (1) traditional semiquantitative criteria (Graham-Appelman criteria), (2) the largest lymphoid aggregate (LA) size-based criteria (Ueno criteria) and (3) LA density-based criteria (Väyrynen-Mäkinen criteria).
Among the three criteria, the Väyrynen-Mäkinen criteria-based CLR assessment showed the best interobserver agreement (κ value, 0.71; intraclass correlation coefficient, 0.76). Pathologically, intense CLR (grade 2) by Graham-Appelman criteria, active CLR (largest LA size ≥1 mm) by Ueno criteria and high-density CLR (≥0.38 LAs/mm) by Väyrynen-Mäkinen criteria significantly correlated with an early cancer stage (stage I/II). In Kaplan-Meier analysis, both CLR statuses determined by Ueno criteria and Väyrynen-Mäkinen criteria were associated with significant differences in disease-free survival in MSI-H CRC patients (p=0.005 and p=0.001, respectively). In multivariable analysis, both active CLR and high-density CLR proved to be independent favourable prognostic factors in MSI-H CRC (HR, 0.47; 95% CI 0.24 to 0.9 for active CLR and HR, 0.5; 95% CI 0.28 to 0.89 for high-density CLR).
Our study confirms that the two recently suggested criteria (Ueno criteria and Väyrynen-Mäkinen criteria) for CLR assessment are fairly reproducible methods and can serve as superior prognosticators in CRC.
结直肠癌（CRC）中的克罗恩样淋巴反应（CLR）与良好的预后及微卫星高度不稳定（MSI-H）状态相关。然而，关于CLR评估的最佳标准尚未达成共识。本研究的目的是对CLR的传统评估标准和新评估标准进行比较验证。
两名病理学家使用三种不同标准独立评估212例MSI-H CRC中的CLR状态：（1）传统半定量标准（Graham-Appelman标准），（2）基于最大淋巴滤泡（LA）大小的标准（Ueno标准），以及（3）基于LA密度的标准（Väyrynen-Mäkinen标准）。
在这三种标准中，基于Väyrynen-Mäkinen标准的CLR评估显示出最佳的观察者间一致性（κ值为0.71；组内相关系数为0.76）。在病理方面，根据Graham-Appelman标准的强烈CLR（2级）、根据Ueno标准的活跃CLR（最大LA大小≥1mm）以及根据Väyrynen-Mäkinen标准的高密度CLR（≥0.38个LA/mm）均与早期癌症阶段（I/II期）显著相关。在Kaplan-Meier分析中，由Ueno标准和Väyrynen-Mäkinen标准确定的CLR状态均与MSI-H CRC患者的无病生存期存在显著差异（p分别为0.005和0.001）。在多变量分析中，活跃CLR和高密度CLR均被证明是MSI-H CRC的独立有利预后因素（活跃CLR的HR为0.47；95%CI为0.24至0.9；高密度CLR的HR为0.5；95%CI为0.28至0.89）。
我们的研究证实，最近提出的两种CLR评估标准（Ueno标准和Väyrynen-Mäkinen标准）是相当可重复的方法，并且可作为CRC中更好的预后指标。
