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Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation.
Modern Pathology ( IF 7.5 ) Pub Date : 2020-02-11 , DOI: 10.1038/s41379-020-0496-1
David S Williams 1, 2, 3 , Dmitri Mouradov 4, 5 , Marsali R Newman 1 , Elham Amini 6 , David K Nickless 7 , Catherine G Fang 2 , Michelle Palmieri 4, 5 , Anuratha Sakthianandeswaren 4, 5 , Shan Li 4 , Robyn L Ward 8, 9 , Nicholas J Hawkins 10, 11 , Iain Skinner 12 , Ian Jones 13 , Peter Gibbs 4, 5, 14, 15 , Oliver M Sieber 4, 5, 16, 17
Affiliation  

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.

中文翻译:

肿瘤浸润淋巴细胞状态优于组织学分级、DNA 错配修复和 BRAF 突变对粘液性分化结直肠腺癌的预后。

粘液性结直肠腺癌 (CRC) 通常定义为细胞外粘蛋白占肿瘤面积的 >50%,而粘蛋白≤50% 的肿瘤被指定为具有粘液成分。然而,这些定义在很大程度上是任意的,并且根据粘液成分的比例对临床分子特征和结果进行比较是有限的。检查了一组 1643 名 II/III 期癌症患者的肿瘤粘液成分、DNA 错配修复 (MMR) 状态、BRAF 突变和肿瘤浸润淋巴细胞 (TIL)。粘液成分≤50% 的肿瘤表现出与粘液肿瘤相似的特征,包括与女性、近端位置、高级别、TIL-高、MMR 缺陷 (dMMR) 和 BRAF 突变相关。粘液成分的比例并未对无病生存期 (DFS) 进行分层。在单变量分析中,dMMR 状态而非组织学分级、粘液性和粘液性成分肿瘤的分层生存;然而,在多变量分析中,dMMR 状态不是独立的预测因子。BRAF 突变的预后价值取决于粘液分化和 MMR 状态,预后不良仅限于非粘液性 pMMR 肿瘤(HR 2.61,95% CI 1.69-4.03;p < 0.001)。TIL 状态是粘液/粘液成分肿瘤 DFS 的一个强有力的独立预测因子(HR 0.40,95% CI 0.23-0.67;p < 0.001),并且与组织学分级、MMR 和 BRAF 突变相比是一个更好的预后预测因子。粘液成分和粘液 II/III 期 CRC 表现出临床分子相似性,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,
更新日期:2020-02-11
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