Department of Pathology, Austin Health, Heidelberg, VIC, Australia.
Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
Mod Pathol. 2020 Jul;33(7):1420-1432. doi: 10.1038/s41379-020-0496-1. Epub 2020 Feb 11.
Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p < 0.001). TIL status was a strong independent predictor of DFS in mucinous/mucinous component tumours (HR 0.40, 95% CI 0.23-0.67; p < 0.001), and a superior predictor of prognosis compared with histological grade, MMR and BRAF mutation. Mucinous component and mucinous stage II/III CRCs exhibit clinico-molecular resemblances, with histological grade and BRAF mutation lacking prognostic value. Prognosis for these tumours was instead strongly associated with TIL status, with the most favourable outcomes in TIL-high dMMR tumours, whilst TIL-low tumours had poor outcomes irrespective of MMR status.
黏液型结直肠癌（CRC）通常定义为肿瘤区域中包含> 50％的细胞外黏蛋白，而黏蛋白含量≤50％的肿瘤则被指定为具有黏蛋白成分。然而，这些定义在很大程度上是任意的，并且通过黏蛋白成分的比例对临床-分子特征和结果进行比较受到限制。对 1643 例 II/III 期癌症患者的肿瘤黏液成分、DNA 错配修复（MMR）状态、BRAF 突变和肿瘤浸润淋巴细胞（TIL）进行了检查。黏蛋白含量≤50％的肿瘤表现出与黏液性肿瘤相似的特征，包括与女性、近端位置、高级别、TIL 高、MMR 缺陷（dMMR）和 BRAF 突变相关。黏液成分的比例并不能分层无病生存（DFS）。在单因素分析中，dMMR 状态，但不是组织学分级，分层了黏液性和黏液性成分肿瘤的生存；然而，在多因素分析中，dMMR 状态不是独立的预测因素。BRAF 突变的预后价值取决于黏液分化和 MMR 状态，不良预后仅限于非黏液性 pMMR 肿瘤（HR 2.61，95％CI 1.69-4.03；p<0.001）。TIL 状态是黏液性/黏液性成分肿瘤 DFS 的一个强有力的独立预测因素（HR 0.40，95％CI 0.23-0.67；p<0.001），并且比组织学分级、MMR 和 BRAF 突变更能预测预后。黏液性成分和黏液性 II/III 期 CRC 具有临床-分子相似性，组织学分级和 BRAF 突变缺乏预后价值。这些肿瘤的预后与 TIL 状态密切相关，在 TIL 高、dMMR 肿瘤中预后最好，而 TIL 低的肿瘤无论 MMR 状态如何，预后均较差。
