Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
AuthorJorissen, RN; Christie, M; Mouradov, D; Sakthianandeswaren, A; Li, S; Love, C; Xu, Z-Z; Molloy, PL; Jones, IT; McLaughlin, S; ...
Source TitleBritish Journal of Cancer
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sLove, Christopher; Mouradov, Dmitri; McLaughlin, Stephen; Lipton, Lara; Gibbs, Peter; Sieber, Oliver; Burgess, Antony; Desai, Jayesh; Jorissen, Robert; Jones, Ian; ...
AffiliationSir Peter MacCallum Department of Oncology
Medical Biology (W.E.H.I.)
Surgery (Western Health)
Document TypeJournal Article
CitationsJorissen, R. N., Christie, M., Mouradov, D., Sakthianandeswaren, A., Li, S., Love, C., Xu, Z. -Z., Molloy, P. L., Jones, I. T., McLaughlin, S., Ward, R. L., Hawkins, N. J., Ruszkiewicz, A. R., Moore, J., Burgess, A. W., Busam, D., Zhao, Q., Strausberg, R. L., Lipton, L. ,... Sieber, O. M. (2015). Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer. BRITISH JOURNAL OF CANCER, 113 (6), pp.979-988. https://doi.org/10.1038/bjc.2015.296.
Access StatusOpen Access
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.
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