Abstract 5175: Advancing the molecular understanding of stage I colorectal cancer

Autor: Philip Dunne, M B. Loughrey, H G. Coleman, R McBride, J Campbell, M Alderdice, K L. Redmond, D G. McArt, C Isella, S Leedham, T Maughan, M Lawler, S:CORT consortium
Rok vydání: 2018
Předmět:
Zdroj: Cancer Research. 78:5175-5175
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2018-5175
Popis: Background: There are ~1.4 million cases of colorectal cancer (CRC) annually worldwide. Bowel cancer screening (BCS) detects cancers and high-risk adenomas earlier; previously stage I accounted for 12% of CRC, but 42% of screen-detected cancers are now stage I. This study is based on the hypothesis that within the early lesions detected by BCS there are "hopeful monsters"; a term used to describe highly aggressive tumours that are simply being caught earlier while they are still potentially curable. Colorectal tumour evolution models have proposed the “Big Bang” of tumour growth, where a single expansion in adenoma development dictates disease outcome. In line with the “hopeful monsters” theory, this model reason that some tumours are “born-to-be-bad” from the earliest point in CRC tumour evolution. Aims: This proposal aims to develop a molecular stratifier of lethal vs non-lethal early-invasive disease based on comprehensive molecular pathological profiling, improved biological understanding and multiple tiers of validation to inform the management of CRC disease at the earliest stage. Methods: In contrast to stage II-IV CRC, there are limited stage I molecular studies, reducing opportunities to identify lethal early-disseminating tumours in patients who account for ~50% of screen-detected cancers. This study is undertaking collection and molecular profiling of a cohort of retrospective stage I tissue (n=200), enriched for patients that experienced relapsed, to identify factors associated with early-dissemination. Results: Pathological characterisation of the stage I cohort indicated that histological factors such as fibroblast content or depth of invasive front are not associated with eventual metastatic relapse. Unsupervised analysis highlighted a detectable shift in transcriptional signalling between recurrent and non-recurrent samples. Further supervised analysis indicates that intrinsic “stem-like” factors may be more prognostic than extrinsic factors in stage I. Conclusions: In order to find any effective treatment you have to first understand the biology underpinning disease. Given the increasing numbers of early stage patients being diagnosed as a result of BCS, and the paucity of tissue cohorts and focussed molecular studies of stage I CRC, this study aims to increase our understanding of specific factors underpinning prognosis at this early stage. Citation Format: Philip Dunne, M B. Loughrey, H G. Coleman, R McBride, J Campbell, M Alderdice, K L. Redmond, D G. McArt, C Isella, S Leedham, T Maughan, M Lawler, S:CORT consortium. Advancing the molecular understanding of stage I colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5175.
Databáze: OpenAIRE
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