Open AccessThe prognostic value of simultaneous tumor and serum RAS / RAF mutations in localized colon cancer
Author(s) -
Thomsen Caroline Emilie B.,
Appelt Ane Lindegaard,
Andersen Rikke Fredslund,
Lindebjerg Jan,
Jensen Lars Henrik,
Jakobsen Anders
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1051
Subject(s) - medicine , colorectal cancer , hazard ratio , mutation , oncology , cancer , multivariate analysis , adenocarcinoma , cancer research , gastroenterology , gene , biology , confidence interval , genetics
The impact of RAS / RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor‐specific DNA , this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I–III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio ( HR ) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact ( P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival ( OS ) ( HR = 2.30, 95% CI = 1.27–4.15, P = 0.0057), and disease‐free survival ( DFS ) ( HR = 2.18, 95% CI = 1.26–3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair ( pMMR ) protein in tumor also indicated significantly worse prognosis, OS ( HR = 3.45, 95% CI = 1.52–7.85, P = 0.0032) and DFS ( HR = 3.61, 95% CI = 1.70–7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS / RAF mutated tumors.