EA4340, Versailles SQY University, Boulogne, France.
Diagn Pathol. 2012 Nov 13;7:156. doi: 10.1186/1746-1596-7-156.
Lymphoid infiltration is a prognostic marker in solid tumors, such as colorectal, breast and lung carcinomas. However, lymphoid infiltration is heterogeneous and the reproducibility of quantification based on single counts within a tumor is very low. We aimed to develop a reproducible method for evaluating lymphoid infiltration in tumors.
Virtual slides were obtained from tissue sections from the localized colorectal carcinomas of 117 patients, stained for CD3 and CD45R0. We assessed the variation of lymphoid cell density by automatic counts in 1 mm-wide, 5 μm-long segments of the invasive front, along an axis 4 mm in length running perpendicular to the invasive front of the tumor.
We plotted curves of the variation of lymphocyte density across the tumor front. Three distinct patterns emerged from this linear quantification of lymphocyte (LQLI). In pattern 1, there was a high density of lymphocytes within the tumor. In pattern 2, lymphocyte density peaked close to the invasive margin. In pattern 3, lymphocytes were diffusely distributed, at low density. It was possible to classify all the tumors studied, and interobserver reproducibility was excellent (kappa =0.9). By contrast, single counts of CD3+ cells on tissue microarrays were highly variable for a given LQLI pattern, confirming the heterogeneity of lymphoid infiltration within individual tumors. In univariate analysis, all pathologic features (stage, metastatic lymph node ratio (LNR), vascular embolism, perineural invasion), CD3+ cell density, LQLI patterns for CD3+ and CD45R0+ cells) were found to have a significant effect on disease-free survival (DFS). In multivariate analysis, only the LQLI pattern for CD3+ cells (HR: 6.02; 95% CI: 2.74-13.18) and metastatic lymph node ratio (HR: 6.14; 95% CI: 2.32-16.2) were associated with DFS.
LQLI is an automated, reproducible method for the assessment of lymphoid infiltration. However, validation of its prognostic value in larger series is required before its introduction into routine practice for prognostic evaluation in patients with colorectal carcinomas.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9861460717895880.
淋巴浸润是结直肠癌、乳腺癌和肺癌等实体瘤的预后标志物。然而，淋巴浸润具有异质性，并且基于肿瘤内的单一计数进行定量的可重复性非常低。我们旨在开发一种可重复的方法来评估肿瘤中的淋巴浸润。
从 117 例局部结直肠癌患者的组织切片中获得虚拟幻灯片，并用 CD3 和 CD45R0 染色。我们评估了沿垂直于肿瘤侵袭前缘的 4 毫米长的轴，在 1 毫米宽、5 微米长的侵袭前缘段内自动计数的淋巴细胞密度变化。
我们绘制了肿瘤前缘淋巴细胞密度变化的曲线。从淋巴细胞的这种线性定量（LQLI）中出现了三种不同的模式。在模式 1 中，肿瘤内淋巴细胞密度较高。在模式 2 中，淋巴细胞密度在靠近侵袭边缘处达到峰值。在模式 3 中，淋巴细胞呈弥漫性低密度分布。可以对所有研究的肿瘤进行分类，并且观察者间的可重复性非常好（kappa = 0.9）。相比之下，给定 LQLI 模式下组织微阵列上的 CD3+细胞的单次计数差异很大，这证实了单个肿瘤内淋巴浸润的异质性。在单因素分析中，所有病理特征（分期、转移性淋巴结比率（LNR）、血管栓塞、神经周围侵犯）、CD3+细胞密度、CD3+和 CD45R0+细胞的 LQLI 模式）均对无病生存率（DFS）有显著影响。在多因素分析中，仅 CD3+细胞的 LQLI 模式（HR：6.02；95%CI：2.74-13.18）和转移性淋巴结比率（HR：6.14；95%CI：2.32-16.2）与 DFS 相关。
LQLI 是一种用于评估淋巴浸润的自动化、可重复的方法。然而，在将其引入常规实践以用于结直肠癌患者的预后评估之前，需要在更大的系列中验证其预后价值。
本文的虚拟幻灯片可在此处找到：http://www.diagnosticpathology.diagnomx.eu/vs/9861460717895880。
