Impact ofRASandBRAFmutations on carcinoembryonic antigen production and pattern of colorectal metastases

Abstract

Author contributions: Fakih M designed and supervised the trial; Fakih M and Cho M wrote the paper; Telatar M, Afkhami M, Sentovich S and Melstrom K contributed to the analysis; Cho M, Akiba C and Lau C collected and analysed data; Smith D did the statistical analysis.Institutional review board statement: This study was reviewed and approved by the City of Hope National Medical Center.Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data. Conflict-of-interest statement:We have no pertinent financial relationships to disclose. METHODS:In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer (CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations. RESULTS:Among 174 patients, mutations in KRAS , NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations (KRAS and NRAS ) were more likely to be found in African American patients (87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA (< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

“…Poor survival outcome of BRAF mutation could be related to its propensity to metastasize frequently to poor prognostic sites like peritoneum and less frequently to liver or lung as seen in this study. However, incidence of peritoneal metastasis in BRAF mutant cancers shows wide variability, ranging from 10 to 45% [12,28]. Although there was no significant association seen between BRAF mutation, bony metastases and brain metastases, the numbers were too small to see any meaningful association.…”

“…In addition, it has been increasingly recognized that biological behavior and prognosis of colorectal cancer may vary according to the location of the primary, BRAF, KRAS and MMR (mismatch repair) status, though data are not consistent [9,11]. Some retrospective analyses suggest these somatic and germ line mutations may have an impact on the pattern of metastasis, but most of these are small, uncontrolled and single institutional studies with varying associations [12,13]. The second part of this study was to investigate any association between molecular markers, site of primary and site of metastasis.…”

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

“…Overall survival, months Survival probability Survival probability Survival probability Survival probability (27,28). The pattern of possible influence of the KRAS mutation on CA 19-9 excretion has not been well established yet.…”

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

“…CEA represents the only conventional and recognized blood-based test for monitoring recurrence and response to systemic therapy in CRC. The superiority of plasma ctDNA assays over CEA are quite evident, with even more applicability in the up to 34% of CEA non-producers in patients with CRC [ 151 ]. Furthermore, several groups have shown that the prognostic potential of ctDNA is independent of known clinicopathologic risk factors.…”