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Title

Combined assessment of the TNM stage and BRAF mutational status at diagnosis in sporadic colorectal cancer patients

AuthorsSayagués, José María ; Carmen, Sofía del; Abad, María del Mar; Corchete, Luis A.; Bengoechea, Óscar; Anduaga, María Fernanda; Baldeón, María Jesús; Cruz, Juan Jesús; Alcazar, Jose Antonio; Angoso, María; González, Marcos ; García, Jacinto; Muñoz-Bellvis, Luís; Orfao, Alberto ; Sarasquete, María Eugenia
KeywordsAnti-EGFR therapy
Colorectal cancer
Prognosis
BRAF V600E mutation
Issue Date2018
PublisherImpact Journals
CitationOncotarget 9(35): 24081-24096 (2018)
AbstractThe prognostic impact of KRAS mutations and other KRAS-related and nonrelated genes such as BRAF, NRAS and TP53, on sporadic colorectal cancer (sCRC) remain controversial and/or have not been fully established. Here we investigated the frequency of such mutations in primary sCRC tumors and their impact on patient progression-free survival (PFS) and overall survival (OS). Primary tumor tissues from 87 sCRC patients were analysed using a custom-built next generation sequencing (NGS) panel to assess the hotspot mutated regions of KRAS/NRAS (exons 2, 3 and 4), BRAF (exon 15) and TP53 (all exons). Overall, mutations in these genes were detected in 46/87 sCRC tumors analyzed (53%) with the following frequencies per gene: TP53, 33%; KRAS, 28%; BRAF, 7%; and NRAS, 1%. A significant association was found between KRAS mutations and right side colon tumor location (p=0.05), well-differentiated tumors (p=0.04) and absence of lymphovascular invasion (p=0.05). In turn, BRAF-mutated tumors frequently corresponded to poorlyor moderately-differentiated sCRC (p=0.02) and showed a higher frequency of peritoneal carcinomatosis (p=0.006) and microsatellite instability (p=0.007). From the prognostic point of view, the BRAF mutational status together with the TNM stage were the only variables that showed an independent adverse impact on patient outcome in the multivariate analyses for both PFS and OS. Based on these results a scoring system was built and patients were classified into three prognostic subgroups with different PFS rates at 2 years: 91% vs. 77% vs. 0%, respectively (p < 0.0001). Additional prospective studies in larger series of sCRC patients where mutations in genes other than those investigated here are required to validate the utility of the proposed predictive model.
Publisher version (URL)https://doi.org/10.18632/oncotarget.25300
URIhttp://hdl.handle.net/10261/169320
Identifiersdoi: 10.18632/oncotarget.25300
e-issn: 1949-2553
Appears in Collections:(IBMCC) Artículos
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