Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation
- Author(s)
- Williams, DS; Mouradov, D; Newman, MR; Amini, E; Nickless, DK; Fang, CG; Palmieri, M; Sakthianandeswaren, A; Li, S; Ward, RL; Hawkins, NJ; Skinner, I; Jones, I; Gibbs, P; Sieber, OM;
- Journal Title
- Modern Pathology
- Publication Type
- Journal epub ahead of print
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 32047231
- Publisher's Version
- https://doi.org/10.1038/s41379-020-0496-1
- NHMRC Grants
- NHMRC/1136119,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-03-20 11:26:20
Last Modified: 2020-03-26 02:26:23