Survey of KRAS, BRAF and PIK3CA mutational status in 209 consecutive Italian colorectal cancer patients

Abstract

Molecular testing for KRAS and BRAF mutations in tumor tissue is a fundamental tool to identify patients with metastatic colorectal cancer (CRC) who are eligible for anti-EGFR monoclonal antibody therapy. We here report a molecular analysis by high-resolution melting analysis and direct sequencing of KRAS, BRAF and PIK3CA hot spot mutations in 209 Italian CRC patients. One hundred and ten patients (51%) were identified who were potentially nonresponders to anti-EGFR therapy: 90/209 patients (43%) harboring KRAS mutations, 13/117 (11.1%) with the V600E BRAF mutation, and 7/209 (3.3%) with mutations in PIK3CA exon 20. The prevalence of BRAF and PIK3CA mutations was significantly higher in patients older than 65 years (p=0.014 and p=0.018), while patients with triple-negative tumors were significantly younger than mutation carriers (p=0.000011). Patients with gene mutations also showed a trend towards preferential tumor location in the colon (p=0.026). Moreover, although involving a relatively small number of samples, we report the presence of a discordant mutational profile between primary tumors and secondary lesions (3/9 patients), suggesting that it is worthwhile to test other available tissues in order to better define the efficacy of targeted therapy. Further correlations of specific clinical features with tumor mutational profile could be helpful to predict the response of CRC patients to monoclonal antibody therapy.

High-Resolution Melting Analysis for accurate detection of BRAF mutations: a systematic review and meta-analysis

“…A total 14 studies1314151617181920212223242526 with 1324 samples were included in our study and the average sample number was 94.5 (range 13 to 201). The earliest study was in March 200515, while the latest was in April 20132526.…”

“…The dye included LCGreen(n = 1), Syto 9(n = 5), LightCycler LC480 High Resolution Melting Master(n = 6),EvaGreen(n = 1),and one study didn't mention about it17. The final volumes (μL) of HRM were 10 μL (n = 8), 20 μL (n = 4), 25 μL (n = 1), while one study didn't mention about it19. The quality of individual studies was relatively high, as all studies met 8 or more of the QUADAS criteria.…”

BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta‐analysis

“…In all, 21 published articles containing data on BRAF and the clinicopathological characteristics were identified [1,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] (Table 1). The search initially identified 2173 studies.…”

BRAFV600E Mutation and Its Association with Clinicopathological Features of Colorectal Cancer: A Systematic Review and Meta-Analysis

“…[11], [13] It was demonstrated that KRAS or BRAF V600E mutations in CRC are associated with clinical resistance to treatment with epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies. [14]–[16] However, the association between the BRAF V600E mutation and the clinicopathological characteristics of CRC remains controversial. [11] Nevertheless, it would be valuable to supplement standard clinical and pathological staging using molecular markers such as KRAS and BRAF V600E to more accurately classify subsets of patients for more effective clinical management.…”