KRAS, NRAS and BRAF mutation profiling in a series of 90 metastasic colorectal cancer spanish patients. An estimation of cost savings.

Rodón Natalia1, Román Ruth1, Verdú Montse1,2, Montes Mª del Mar3, García-Peláez Beatriz1, Diaz Olga1, Lacasa Carmen3 and Puig Xavier1,2.

1 BIOPAT. Biopatologia Molecular S.L., Barcelona (Spain). 2 HISTOPAT Laboratoris S.L., Barcelona (Spain). 3 Departamento de Farmacia. Hospital de Barcelona (SCIAS), Grup Assistència, Barcelona (Spain).

Background: Metastasic colorectal cancer (mCRC) patients harbouring a mutation in codon 12 or 13 of the KRAS does not benefit from therapy with antibodies targeting epidermal growth factor receptor (EGFR). Recently, several studies have shown that an extended study of the RAS family genes (KRAS exons 3 and 4; and NRAS exons 2, 3 and 4) could help to detect those patients that although having a wild-type KRAS exon 2 will not respond to anti-EGFR treatment. The aim of this study was to assess the KRAS, NRAS and BRAF mutational profiling in a series of spanish patients with mCRC and to extrapolate these results to the economic implications of a better triage.

Design: 90 mCRC were included in a prospective study from December 2013 to August 2014. DNA was extracted from formalin-fixed paraffin embedded sections. Mutations in exon 2 (codons 12 and 13) of KRAS and BRAF V600E mutation were analized with KRAS-BRAFStripAssay℗ (Viennalab). Further mutations in KRAS exon 3 and 4 and exons 2, 3 and 4 of NRAS were tested when no mutation in KRAS exon 2 was found. The extended study was performed as well in those cases with a G13D mutation (a proposed predictive marker of response to anti-EGFR). KRAS exon 3 and 4 (codons 59, 61, 117 and 146) were analized using RAS extension Pyro℗ Kit (Qiagen). NRAS mutations in exon 2 (codons 12 and 13), 3 (codon 59 and 61) and 4 (codons 117 and 147) were analized using the Therascreen℗ NRAS Pyro℗ kit and RAS extension Pyro℗ Kit (Qiagen). In our Hospital the median cost per month of a treatment with anti-EGFR is 2.000€ and the median progression-free survival is 8 months.

Results: Thirty-six (40%) cases had a mutation in KRAS exon 2. Fifty-three (58,9%) were native and were tested with the extended study together with 5 cases that carried a G13D mutation. None of the G13D cases had another mutation. Nine (17%) of the 53 KRAS exon 2 native cases had a mutation in another exon of KRAS or NRAS. Eight (8,9%) cases had V600E mutation in BRAF, no other mutation was identified. In 1 (1,1%) case a valid result was not achieved.

Conclusions: In this series the implementation of the RAS extended study allows the identification of a further 17% of the KRAS exon 2 native patients that will not respond to anti-EGFR therapy; supposing a saving of 144.000€. The global percentage of patients with a mutation in a RAS family gene arises to 57%.

Texto completo

Abstract exhibited at the:


Abstract in Modern Pathology 2015; 28 suplement 2: 187A.