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  -