Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
Journal Title
Br J Cancer
Publication Type
Journal Article
Abstract
BACKGROUND: APC mutations (APC-mt) occur in approximately 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 HR1.79, P0.015; RFS HR1.88, P0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P0.036). 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 HR2.50, P0.010; RFS HR2.14, P0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.British Journal of Cancer advance online publication 25 August 2015; doi:10.1038/bjc.2015.296 www.bjcancer.com.
Publisher
NPG
WEHI Research Division(s)
Systems Biology And Personalised Medicine; Structural Biology
PubMed ID
26305864
Rights Notice
This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License.


Creation Date: 2015-09-01 03:55:19
Last Modified: 2018-03-16 02:28:09
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