Influence of Somatic Mutations of Kras, Nras, Braf and Microsatellite Instability Status on Survival of Colorectal Cancer Patients With Peritonal Carcino

Abstract

Purpose: to evaluate the effect of somatic mutations of the KRAS, NRAS, BRAF genes and the status of microsatellite instability on the overall and disease-free survival of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Material and Methods. From 2012 to 2018, the study included 45 patients who underwent surgery for synchronous peritoneal carcinomatosis with colorectal cancer. In all patients, mutations of the KRAS, NRAS, BRAF genes and MSI status of the tumor and peritoneum metastases were determined using Sanger sequencing, fragment analysis and digital droplet polymerase chain reaction. The effect of mutations on patient survival was evaluated.Results. The prevalence of somatic mutations was 69 % of patients. The discordance between the tumor and peritoneum metastases was 9 %. All tumors and peritoneum metastases were microsatellite stable. KRAS, NRAS, BRAF mutations did not affect the overall and disease-free survival (p=0.87 and p=0.85, respectively).Conclusion. Somatic mutations in the KRAS, NRAS, or BRAF genes are not a prognostic factor affecting the overall and relapse-free survival of colorectal cancer patients with peritoneal carcinomatosis. The molecular status of primary tumor may differ from the status of peritoneal metastasis. It should be taken into account when prescribing targeted drugs.

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

“…It is known that clinical features of CRC patients with mutations in the BRAF gene are predominantly female gender and older age [4,5,7,8]. In our study, the females also prevail, while the number of male patients was twice as small (Table 2).…”

“…In addition, it is quite lower, but not significantly, than the data obtained from the patients in Germany 8% (160/1,995) and Japan -8.7% (41/472) (p > 0.05; Table 3) [15,19]. These differences can be explained by the fact that life expectancy in these countries is higher than in Russia, as it is well known that BRAF mutations are mainly found in elderly patients [5,8].…”

“…Several cancer groups are distinguished depending on these markers. Thus, a mutation in the BRAF gene accounts for approximately 10% of all cases of CRC [5,6] and BRAF mutated CRC is more likely associated with elderly age, female gender, proximal tumor location, as well as a low tumor differentiation [4,7,8].…”