Histological scoring of immune and stromal features in breast and axillary lymph nodes is prognostic for distant metastasis in lymph node-positive breast cancers
Histological scoring of immune and stromal features in breast and axillary lymph nodes is prognostic for distant metastasis in lymph node-positive breast cancers
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DOI：
10.1002/cjp2.87
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发表时间：
2018-01-01
影响因子：
4.1
通讯作者：
Pinder, Sarah E.
中科院分区：
文献类型：
--
作者：
Grigoriadis, Anita;Gazinska, Patrycja;Pinder, Sarah E.
淋巴结 (LN) 状态和肿瘤浸润淋巴细胞 (TIL) 的预后重要性已得到充分证实，特别是 TIL 在三阴性乳腺癌 (TNBC) 中。到目前为止，很少有研究询问受累和未受累淋巴结的变化，并评估它们的形态模式是否为预测乳腺癌疾病进展提供了有价值的信息。在一组富含 TNBC 的 309 名患者 (170/309) 中，我们在常规苏木精和伊红染色切片上对原发性肿瘤以及相关受累和未受累腋窝淋巴结进行组织学表征。在 309 名患者中，143 名患有 LN 阳性疾病。评估了 25 种组织病理学特征，包括 TIL 存在程度、生发中心 (GC) 和窦组织细胞增多症的定量和定性评估。使用多变量和交叉验证的比例风险回归分析来确定预测无远处转移生存（DMFS）的最佳协变量集。瘤内和瘤周免疫浸润的程度与未受累和受累淋巴结的结构变化相关。通过将临床病理学特征以及肿瘤和 LN 组织病理学特征纳入 L2 正则比例风险模型，所有癌症和 TNBC 的 5 年 DMFS 预测比基线提高了 3-15%。在 LN 阳性癌症中，萨尔加多分类、淋巴细胞小叶炎、未受累 LN 中 GC 的大小和数量以及受累 LN 中 GC 位置的组合具有重要的预后信息。根据这些特征，构建了一个多变量交叉验证稳定的风险特征，该特征确定了 LN 阳性乳腺癌和 LN 阳性 TNBC 组中的低风险组，其 10 年 DMFS 概率分别为 78% 和 87%。这项研究表明，通过将受累和未受累淋巴结的组织病理学模式与原发肿瘤免疫和基质特征相结合，可以更准确地预测淋巴结阳性乳腺癌发生远处转移的情况。
The prognostic importance of lymph node (LN) status and tumour-infiltrating lymphocytes (TILs), is well established, particularly TILs in triple negative breast cancers (TNBCs). So far, few studies have interrogated changes in involved and uninvolved LNs and evaluated if their morphological patterns add valuable information for the prediction of disease progression in breast cancer. In a cohort of 309 patients enriched for TNBCs (170/309), we histologically characterised immune and stromal features in primary tumours and associated involved and uninvolved axillary LNs on routine haematoxylin and eosin stained sections. Of the 309 patients, 143 had LN-positive disease. Twenty-five histopathological features were assessed, including the degree of TIL presence, quantitative and qualitative assessment of germinal centres (GCs) and sinus histiocytosis. Multivariate and cross-validated proportional hazard regression analyses were used to identify optimal covariate sets for prediction of distant metastasis-free survival (DMFS). The degree of intratumoural and peritumoural immune infiltrate was associated with architectural changes in both uninvolved and involved LNs. By including clinicopathological characteristics as well as tumour and LN histopathological features in L2-regularised proportional hazard models, the prediction of 5-year DMFS was improved by 3-15% over the baseline in all cancers and in TNBCs. In LN-positive cancers, the combination of Salgado's classification, lymphocytic lobulitis, size and number of GCs in the uninvolved LNs and location of GCs in the involved LNs carried significant prognostic information. From these features, a multivariate cross-validation-stable risk signature was constructed, which identified low-risk groups within both LN-positive breast cancers and the LN-positive TNBCs group with a 10-year DMFS probability of 78 and 87%, respectively. This study illustrates that, by incorporating histopathological patterns of involved and uninvolved LNs combined with primary tumour immune and stromal features, the prediction of developing distant metastasis in LN-positive breast cancers can be estimated more accurately.