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|Title:||Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer|
|Citation:||British Journal of Cancer, 2015; 113(6):979-988|
|Publisher:||Nature Publishing Group|
|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|
|Appears in Collections:||Medicine publications|
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