Kloft Maximilian, Budginaite Elzbieta, van Kuijk Sander M J, Raghuram Gayatri, Magee Derek R, Nankivell Matthew G, Cunningham David, Allum William H, Langley Ruth E, Grabsch Heike I
Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands; Institute of Clinical Cancer Research, Krankenhaus Nordwest, Frankfurt, Germany.
Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Precision Medicine, GROW - Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
Pathol Res Pract. 2025 Feb;266:155818. doi: 10.1016/j.prp.2025.155818. Epub 2025 Jan 8.
Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host's anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.
To investigate the hypotheses: (1) the host anti-tumour immune response is similar in all LNneg from an individual OeC patient reflected in a similar microarchitecture in all LNneg; and (2) immune response measured in the largest LNneg can represent that of all LNnegs.
(y)pN0 patients from the Oe02 trial with at least two LNneg were included. Microarchitectural LN features (germinal centres (GermC), lymphocytes outside GermCs (lymphocytes), histiocytes) were morphometrically quantified. Linear mixed-effects models, intraclass correlation coefficients (ICC) and Bland-Altman plots were used to determine systematic bias, reliability/variability and agreement of LNneg microarchitecture measurements.
Linear mixed-effects models showed no systematic bias in LNneg microarchitectural features within a patient. The ICC revealed moderate variability for lymphocytes (ICC: 0.39; 95 %CI: 0.01- 0.61, p = 0.02)) and GermC (ICC: 0.50; 95 %CI: 0.22-0.68, p < 0.001), and high variability for histiocytes (ICC: 0.07 (95 %CI: -0.45-0.40, p = 0.38). Bland-Altman plots showed that 5.0 % of GermC, 5.0 % of histiocytes and 8.5 % of lymphocyte measurements were outside the 95 % limits of agreement.
This is the first study to systematically assess agreement of microarchitectural features in LNneg within an individual (y)pN0 OeC patient. The absence of systematic bias supports using largest LNneg as surrogate for OeC patient's overall anti-tumour immune response.
区域淋巴结（LN）状态是食管癌（OeC）的关键预后因素。肿瘤衍生抗原可激活淋巴结中的免疫反应，这可能反映宿主的抗肿瘤免疫反应。目前尚不清楚在个体OeC患者的所有肿瘤阴性淋巴结（LNneg）中这种反应是否一致。
研究以下假设：（1）个体OeC患者所有LNneg中的宿主抗肿瘤免疫反应相似，表现为所有LNneg中具有相似的微观结构；（2）在最大的LNneg中测量的免疫反应可代表所有LNneg的免疫反应。
纳入Oe02试验中至少有两个LNneg的（y）pN0患者。对淋巴结的微观结构特征（生发中心（GermC）、生发中心外的淋巴细胞（淋巴细胞）、组织细胞）进行形态计量学量化。使用线性混合效应模型、组内相关系数（ICC）和Bland-Altman图来确定LNneg微观结构测量的系统偏差、可靠性/变异性和一致性。
线性混合效应模型显示患者体内LNneg微观结构特征无系统偏差。ICC显示淋巴细胞（ICC：0.39；95%CI：0.01 - 0.61，p = 0.02）和GermC（ICC：0.50；95%CI：0.22 - 0.68，p < 0.001）具有中等变异性，组织细胞具有高变异性（ICC：0.07（95%CI：-0.45 - 0.40，p = 0.38）。Bland-Altman图显示，5.0%的GermC、5.0%的组织细胞和8.5%的淋巴细胞测量值超出了95%一致性界限。
这是第一项系统评估个体（y）pN0 OeC患者LNneg微观结构特征一致性的研究。无系统偏差支持将最大的LNneg用作OeC患者总体抗肿瘤免疫反应的替代指标。
