69P - Next generation sequencing in colorectal cancer: Association of BRAF, KRAS mutations with right sided cancers, mucinous disease, lymphovascular/perineural invasion and microsatellite instability

Background

Colorectal cancer is one of the commonest malignancies worldwide. Next Generation Sequencing (NGS) helps inform treatment pathways for patients post surgery, and also provides valuable information regarding genetic mutations in cancer, the pathogenesis and biology of the disease. We reviewed NGS mutation profiling in our colorectal cancer patients.

Methods

NGS analysis was performed over a 7 year period. Data retrieved from medical records and pathology reports.

Results

92 patients underwent surgery for colorectal cancer during the study period. Mean age: 71 years (Range:44-87). M:F: 1.05:1 43 patients (46.7%) were found to have mutations on NGS sequencing. No significant difference in age, sex, tumour size, lymph node ratio or stage at presentation between the two groups. NGS mutation was significantly associated with right sided disease (p=0.01, Fishers exact test), and this association was highly significant for the BRAF V600e mutation (p=0.0001), NGS mutation was significantly associated with mucinous disease (p=0.04), lymphovascular and / or perineural invasion (p=0.02), and microsatellite instability (p=0.0136), but not metastatic disease at presentation (p=1). Kaplan Meier survival analysis revealed no difference in survival between patients with NGS mutations and those without (p=0.52) or on any subset analysis. COX proportional hazards testing revealed only a significant relationship between tumour size and survival in all patients on multivariate analysis (p=0.002).

Conclusions

NGS sequencing provides relevant information regarding the association of cancers with aggressive features and microsatellite instability. Association of the BRAF mutation with right sided colon cancers has been described previously and may reflect a different pathway to carcinogenesis in the right colon, which has been postulated to have a different origin to the left colon. Significant association of gene mutations with microsatellite instability, but no difference in metastatic disease and overall survival may relect better immune response to these tumours, MSI has been observed to be associated with reduced risk of metastasis.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.