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Abstract：
BACKGROUND: To implement the new marker in clinical practice, reliability assessment, validation, and standardization of utilization must be applied. This study evaluated the reliability of tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) assessment through conventional microscopy by comparing observers\' estimations.
METHODS: Intratumoral and tumor-front stromal TILs, and TSR, were assessed by three pathologists using 86 CRC HE slides. TSR and TILs were categorized using one and four different proposed cutoff systems, respectively, and agreement was assessed using the intraclass coefficient (ICC) and Cohen\'s kappa statistics. Pairwise evaluation of agreement was performed using the Fleiss kappa statistic and the concordance rate and it was visualized by Bland-Altman plots. To investigate the association between biomarkers and patient data, Pearson\'s correlation analysis was applied.
RESULTS: For the evaluation of intratumoral stromal TILs, ICC of 0.505 (95% CI: 0.35-0.64) was obtained, kappa values were in the range of 0.21 to 0.38, and concordance rates in the range of 0.61 to 0.72. For the evaluation of tumor-front TILs, ICC was 0.52 (95% CI: 0.32-0.67), the overall kappa value ranged from 0.24 to 0.30, and the concordance rate ranged from 0.66 to 0.72. For estimating the TSR, the ICC was 0.48 (95% CI: 0.35-0.60), the kappa value was 0.49 and the concordance rate was 0.76. We observed a significant correlation between tumor grade and the median of TSR (0.29 (95% CI: 0.032-0.51), p-value = 0.03).
CONCLUSIONS: The agreement between pathologists in estimating these markers corresponds to poor-to-moderate agreement; implementing immune scores in daily practice requires more concentration in inter-observer agreements.
METHODS: Intratumoral and tumor-front stromal TILs, and TSR, were assessed by three pathologists using 86 CRC HE slides. TSR and TILs were categorized using one and four different proposed cutoff systems, respectively, and agreement was assessed using the intraclass coefficient (ICC) and Cohen\'s kappa statistics. Pairwise evaluation of agreement was performed using the Fleiss kappa statistic and the concordance rate and it was visualized by Bland-Altman plots. To investigate the association between biomarkers and patient data, Pearson\'s correlation analysis was applied.
RESULTS: For the evaluation of intratumoral stromal TILs, ICC of 0.505 (95% CI: 0.35-0.64) was obtained, kappa values were in the range of 0.21 to 0.38, and concordance rates in the range of 0.61 to 0.72. For the evaluation of tumor-front TILs, ICC was 0.52 (95% CI: 0.32-0.67), the overall kappa value ranged from 0.24 to 0.30, and the concordance rate ranged from 0.66 to 0.72. For estimating the TSR, the ICC was 0.48 (95% CI: 0.35-0.60), the kappa value was 0.49 and the concordance rate was 0.76. We observed a significant correlation between tumor grade and the median of TSR (0.29 (95% CI: 0.032-0.51), p-value = 0.03).
CONCLUSIONS: The agreement between pathologists in estimating these markers corresponds to poor-to-moderate agreement; implementing immune scores in daily practice requires more concentration in inter-observer agreements.
摘要：
背景：为了在临床实践中实施新的标记，可靠性评估，验证,必须应用标准化利用。这项研究通过比较观察者的估计，通过常规显微镜评估了肿瘤浸润淋巴细胞（TIL）和肿瘤基质比（TSR）评估的可靠性。
方法：肿瘤内和肿瘤前间质TILs，和TSR,由三名病理学家使用86张CRCHE载玻片进行评估。TSR和TIL使用一种和四种不同的拟议截止系统进行了分类，分别,使用组内系数(ICC)和科恩的卡帕统计数据评估一致性。使用Fleisskappa统计量和一致率对协议进行成对评估，并通过Bland-Altman地块进行可视化。为了研究生物标志物和患者数据之间的关联，采用Pearson相关分析。
结果：对于肿瘤内基质TILs的评估，ICC为0.505（95%CI：0.35-0.64），kappa值在0.21至0.38的范围内，一致率在0.61至0.72的范围内。对于肿瘤前TILs的评估，ICC为0.52（95%CI：0.32-0.67），总体kappa值范围为0.24~0.30,一致率范围为0.66~0.72.为了估计TSR，ICC为0.48（95%CI：0.35-0.60），kappa值为0.49，一致率为0.76。我们观察到肿瘤分级与TSR中位数之间存在显着相关性（0.29（95％CI：0.032-0.51），p值=0.03)。
结论：病理学家在评估这些标志物时的一致性对应于差到中等的一致性；在日常实践中实施免疫评分需要更多的观察者间协议。
方法：肿瘤内和肿瘤前间质TILs，和TSR,由三名病理学家使用86张CRCHE载玻片进行评估。TSR和TIL使用一种和四种不同的拟议截止系统进行了分类，分别,使用组内系数(ICC)和科恩的卡帕统计数据评估一致性。使用Fleisskappa统计量和一致率对协议进行成对评估，并通过Bland-Altman地块进行可视化。为了研究生物标志物和患者数据之间的关联，采用Pearson相关分析。
结果：对于肿瘤内基质TILs的评估，ICC为0.505（95%CI：0.35-0.64），kappa值在0.21至0.38的范围内，一致率在0.61至0.72的范围内。对于肿瘤前TILs的评估，ICC为0.52（95%CI：0.32-0.67），总体kappa值范围为0.24~0.30,一致率范围为0.66~0.72.为了估计TSR，ICC为0.48（95%CI：0.35-0.60），kappa值为0.49，一致率为0.76。我们观察到肿瘤分级与TSR中位数之间存在显着相关性（0.29（95％CI：0.032-0.51），p值=0.03)。
结论：病理学家在评估这些标志物时的一致性对应于差到中等的一致性；在日常实践中实施免疫评分需要更多的观察者间协议。
