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Title: Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation.
Austin Authors: Williams, David S ;Mouradov, Dmitri;Newman, Marsali R ;Amini, Elham;Nickless, David K;Fang, Catherine G;Palmieri, Michelle;Sakthianandeswaren, Anuratha;Li, Shan;Ward, Robyn L;Hawkins, Nicholas J;Skinner, Iain;Jones, Ian;Gibbs, Peter;Sieber, Oliver M
Affiliation: Clinipath Pathology, Sonic Healthcare, Perth, WA, Australia
Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
Department of Surgery, Western Health, Footscray, VIC, Australia
Melbourne Pathology, Cabrini Health, Malvern, VIC, Australia
Department of Pathology, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia
Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
Prince of Wales Clinical School and Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia
Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia
Faculty of Medicine, The University of Queensland, Herston, QLD, Australia
Department of Medical Oncology, Parkville, VIC, Australia
Department of Medical Oncology, Western Health, Footscray, VIC, Australia
Department of Surgery, The University of Melbourne, Parkville, VIC, Australia
School of Biomedical Sciences, Monash University, Clayton, VIC, Australia
Issue Date: Jul-2020
Date: 2020-02-11
Publication information: Modern Pathology 2020; 33(7): 1420-1432
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.
DOI: 10.1038/s41379-020-0496-1
ORCID: 0000-0001-9480-0786
Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
PubMed URL: 32047231
Type: Journal Article
Appears in Collections:Journal articles

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