Phenotype-Genotype Correlation in Colorectal Cancer: A Real-Life Study

Abstract

<b><i>Background and Aims:</i></b> Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype. <b><i>Methods:</i></b> Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. <i>RAS</i> and <i>BRAF</i> mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis. <b><i>Results:</i></b> Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). <i>RAS</i>-mutated tumours were associated with reduced DFS (<i>p</i> = 0.02) and OS (<i>p</i> = 0.045) in stage I–III CRC. <i>BRAF</i>-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I–III disease. However, after relapse, length of survival was 3.5 months in <i>BRAF</i>-mutated tumours in contrast to 18.6 months in <i>BRAF</i> wild-type tumours (<i>p</i> = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (<i>RAS, BRAF</i> and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study. <b><i>Conclusion:</i></b> In our cohort, <i>RAS</i>-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.