Background:It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status.Methods: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAFc.1799T>A mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC.Results:Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF c.1799T>A mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77).Conclusion:Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.

Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia / A. Malesci, G. Basso, P. Bianchi, L. Fini, F. Grizzi, G. Celesti, G. Di Caro, G. Delconte, F. Dattola, A. Repici, M. Roncalli, M. Montorsi, L. Laghi. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - 110:5(2014 Mar), pp. 1228-1235. [10.1038/bjc.2013.827]

Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia

A. Malesci
;
G. Celesti;G. Delconte;F. Dattola;M. Roncalli;
2014-03

Abstract

Background:It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status.Methods: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAFc.1799T>A mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC.Results:Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF c.1799T>A mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77).Conclusion:Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.
Island methylator phenotype; microsatellite instability; DNA methylation; colon cancers; braf mutation; carcinoma; timors; prevalence; adenomas; features
Settore MED/12 - Gastroenterologia
Settore MED/09 - Medicina Interna
16-gen-2014
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/325607
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