Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer

Jorissen, Robert N., Christie, Michael, Mouradov, Dmitri, Sakthianandeswaren, Anuratha, Li, Shan, Love, Christopher, Xu, Zheng-Zhou, Molloy, Peter L., Jones, Ian T., McLaughlin, Stephen, Ward, Robyn L., Hawkins, Nicholas J., Ruszkiewicz, Andrew R., Moore, James, Burgess, Antony W., Busam, Dana, Zhao, Qi, Strausberg, Robert L., Lipton, Lara, Desai, Jayesh, Gibbs, Peter and Sieber, Oliver M. (2015) Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer. BJC, 113 6: 979-988. doi:10.1038/bjc.2015.296


Author Jorissen, Robert N.
Christie, Michael
Mouradov, Dmitri
Sakthianandeswaren, Anuratha
Li, Shan
Love, Christopher
Xu, Zheng-Zhou
Molloy, Peter L.
Jones, Ian T.
McLaughlin, Stephen
Ward, Robyn L.
Hawkins, Nicholas J.
Ruszkiewicz, Andrew R.
Moore, James
Burgess, Antony W.
Busam, Dana
Zhao, Qi
Strausberg, Robert L.
Lipton, Lara
Desai, Jayesh
Gibbs, Peter
Sieber, Oliver M.
Title Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
Formatted title
Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
Journal name BJC   Check publisher's open access policy
ISSN 1532-1827
0007-0920
Publication date 2015-09
Year available 2015
Sub-type Article (original research)
DOI 10.1038/bjc.2015.296
Open Access Status DOI
Volume 113
Issue 6
Start page 979
End page 988
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword APC
Mutation
Prognosis
Colorectal cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 02 Aug 2016, 15:17:20 EST by Amelie Casgrain on behalf of School of Medicine