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- Title
Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer.
- Authors
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
- Abstract
<bold>Background: </bold>APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.
- Subjects
COLON cancer diagnosis; ADENOMATOUS polyposis coli genetic testing; MICROSATELLITE repeats; CPG nucleotides; DNA methylation; CANCER relapse; COLON tumors; DEGENERATION (Pathology); DNA; ONCOGENES; PHOSPHOTRANSFERASES; PROGNOSIS; TRANSFERASES; PROTEIN microarrays
- Publication
British Journal of Cancer, 2015, Vol 113, Issue 6, p979
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2015.296