Department of Pathology, University of Oulu, Finland; Oulu University Hospital Oulu, Finland, and Medical Research Center Oulu, Finland.
Int J Cancer. 2014 May 1;134(9):2126-35. doi: 10.1002/ijc.28533. Epub 2013 Oct 24.
A subset of colorectal cancers (CRCs) exhibits so-called Crohn's like lymphoid reaction (CLR), an inflammatory reaction pattern that consists of numerous transmural lymphoid aggregates. However, the composition of these aggregates, their biological mechanisms and their prognostic significance are not well-defined. We analyzed two CRC cohorts (418 and 149 patients) and determined clinicopathological features including survival. A new method for evaluating CLR based on counting the areal density of the lymphoid follicles (CLR density) was adopted. Immune cell densities at intratumoral and peritumoral regions, as well as the composition of the lymphoid follicles, were studied by immunohistochemistry. We found that CLR comprised of lymphoid aggregates with no evidence of granuloma formation. High CLR density associated with lower tumor stage, lack of preoperative radiotherapy or chemoradiotherapy and deficient mismatch repair enzyme expression. CLR density had positive correlations with peritumoral and intratumoral densities of CD83(+) mature dendritic cells and T cells. High CLR density associated with better survival and had prognostic value that was independent of stage, Klintrup-Mäkinen score for peritumoral inflammation and the numbers of tumor infiltrating T cells. CLR density evaluation had excellent intraobserver and interobserver agreement. In conclusion, the results suggest that CLR contributes to the adaptive antitumor immunity. Quantitative evaluation of CLR density is a relevant prognostic indicator in CRC.
一部分结直肠癌（CRC）表现出所谓的克罗恩样淋巴反应（CLR），这是一种炎症反应模式，由大量穿壁性淋巴聚集组成。然而，这些聚集的组成、它们的生物学机制及其预后意义尚不清楚。我们分析了两个 CRC 队列（418 例和 149 例患者），并确定了包括生存在内的临床病理特征。采用了一种基于计数淋巴滤泡面积密度（CLR 密度）的评估 CLR 的新方法。通过免疫组织化学研究了肿瘤内和肿瘤周围区域的免疫细胞密度以及淋巴滤泡的组成。我们发现 CLR 由无肉芽肿形成证据的淋巴聚集组成。高 CLR 密度与肿瘤分期较低、缺乏术前放疗或放化疗以及错配修复酶表达缺陷有关。CLR 密度与肿瘤周围和肿瘤内 CD83(+)成熟树突状细胞和 T 细胞的密度呈正相关。高 CLR 密度与更好的生存相关，且具有独立于分期、肿瘤周围炎症的 Klintrup-Mäkinen 评分以及肿瘤浸润 T 细胞数量的预后价值。CLR 密度评估具有出色的观察者内和观察者间一致性。总之，这些结果表明 CLR 有助于适应性抗肿瘤免疫。CLR 密度的定量评估是 CRC 的一个相关预后指标。
