Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes.


Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
03 2019
Historique:
received: 13 11 2017
revised: 17 12 2017
accepted: 28 12 2017
pubmed: 1 2 2018
medline: 14 7 2020
entrez: 1 2 2018
Statut: ppublish

Résumé

Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear. A prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and Tumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; P TIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.

Identifiants

pubmed: 29382774
pii: gutjnl-2017-315664
doi: 10.1136/gutjnl-2017-315664
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

465-474

Informations de copyright

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

David S Williams (DS)

Department of Pathology, Austin Health, Heidelberg, Victoria, Australia.
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.

Dmitri Mouradov (D)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Robert N Jorissen (RN)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Marsali R Newman (MR)

Department of Pathology, Austin Health, Heidelberg, Victoria, Australia.

Elham Amini (E)

Clinipath Pathology, Sonic Healthcare, Perth, Western Australia, Australia.

David K Nickless (DK)

Australian Clinical Labs, The Northern Hospital, Epping, Victoria, Australia.

Julie A Teague (JA)

Australian Clinical Labs, The Northern Hospital, Epping, Victoria, Australia.

Catherine G Fang (CG)

Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.

Michelle Palmieri (M)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Marie J Parsons (MJ)

Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Anuratha Sakthianandeswaren (A)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Shan Li (S)

Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Robyn L Ward (RL)

Office of the Deputy Vice-Chancellor (Research), The University of Queensland, Brisbane, Queensland, Australia.

Nicholas J Hawkins (NJ)

Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Ian Faragher (I)

Department of Surgery, Western Health, Footscray, Australia.

Ian T Jones (IT)

Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Peter Gibbs (P)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Oncology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Oncology, Western Health, Footscray, Victoria, Australia.

Oliver M Sieber (OM)

Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia.
School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.

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