Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
Menée sur 746 patients atteints d'un cancer colorectal de stade I à IV, cette étude met en évidence un pronostic défavorable chez les patients atteints d'une tumeur située dans la région proximale du côlon et ne présentant pas de mutation du gène APC et d'instabilité microsatellitaire
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 HRgreater than or equal to1.79, Pless than or equal to0.015; RFS HRgreater than or equal to1.88, Pless than or equal to0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (Pless than or equal to0.036). 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 HRgreater than or equal to2.50, Pless than or equal to0.010; RFS HRgreater than or equal to2.14, Pless than or equal to0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (Pless than or equal to0.016).
Conclusions : APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.
British Journal of Cancer , résumé, 2014