Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/103716
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer |
Author: | Jorissen, R. Christie, M. Mouradov, D. Sakthianandeswaren, A. Li, S. Love, C. Xu, Z. Molloy, P. Jones, I. McLaughlin, S. Ward, R. Hawkins, N. Ruszkiewicz, A. Moore, J. Burgess, A. Busam, D. Zhao, Q. Strausberg, R. Lipton, L. Desai, J. et al. |
Citation: | British Journal of Cancer, 2015; 113(6):979-988 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | Robert N Jorissen, Michael Christie, Dmitri Mouradov, Anuratha Sakthianandeswaren, Shan Li, Christopher Love, Zheng-Zhou Xu, Peter L Molloy, Ian T Jones, Stephen McLaughlin, Robyn L Ward, Nicholas J Hawkins, Andrew R Ruszkiewicz, James Moore, Antony W Burgess, Dana Busam, Qi Zhao, Robert L Strausberg, Lara Lipton, Jayesh Desai, Peter Gibbs, and Oliver M Sieber |
Abstract: | BACKGROUND: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. METHODS: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer. |
Keywords: | APC; mutation; prognosis; colorectal cancer |
Rights: | © 2015 Cancer Research UK. All rights reserved |
DOI: | 10.1038/bjc.2015.296 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1062226 |
Published version: | http://dx.doi.org/10.1038/bjc.2015.296 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.