TY - JOUR AU - Jorissen, RN AU - Christie, M AU - Mouradov, D AU - Sakthianandeswaren, A AU - Li, S AU - Love, C AU - Xu, Z-Z AU - Molloy, PL AU - Jones, IT AU - McLaughlin, S AU - Ward, RL AU - Hawkins, NJ AU - Ruszkiewicz, AR AU - Moore, J AU - Burgess, AW AU - Busam, D AU - Zhao, Q AU - Strausberg, RL AU - Lipton, L AU - Desai, J AU - Gibbs, P AU - Sieber, OM Y2 - 2020/12/22 Y1 - 2015/09/15 SN - 0007-0920 UR - http://hdl.handle.net/11343/257698 AB - 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. LA - English PB - NATURE PUBLISHING GROUP T1 - Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer DO - 10.1038/bjc.2015.296 IS - British Journal of Cancer VL - 113 IS - 6 SP - 979-988 L1 - /bitstream/handle/11343/257698/PMC4578087.pdf?sequence=1&isAllowed=y ER -