Somatic mutation status in aCRC is becoming increasingly relevant as it may predict efficacy of biological therapies but also site-specific patterns of metastatic spread and outcome.
We retrospectively analysed a cohort of 640 consecutive aCRC pts diagnosed at University Hospital of Udine, Italy, from 1st January 2000 to 15th March 2017. KRAS, NRAS, BRAF and PIK3CA status was all locally determined by pyrosequencing and/or mass-Spectrometry Assay, with commercially available kits (diatech pharmacogenetics). Pearson’s Χ2 test was performed with uni- and multivariate models to test association of mutational status and site-specific metastatic spread at the time of diagnosis, death or last follow-up.
Overall, we detected 283 (47%) KRAS mutations, 21 (4%) NRAS mutations, 40 (7%) BRAF mutations, and 61 (14%) PIK3CA mutations. Most common mutations in KRAS gene were located in exon 2 (86%), while about 3% of mutations involved exon 3 and 5% exon 4. NRAS mutations involved equally exons 2 and 3. All BRAF mutated tumours except for one, exhibited exon 15 V600E mutations. Pts with KRAS mutations had an increased risk to develop lung metastases (odds ratio, OR 2.56, 95% CI 1.76-3.71; p
Our findings suggest that molecular biology may help predicting the metastatic spread in aCRC pts. If confirmed by further studies, these observations could translate into tailored surveillance and follow-up protocols.
Clinical trial identification
Legal entity responsible for the study
University and General Hospital of Udine, Italy
All authors have declared no conflicts of interest.