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Prognostic impact of mutations and allele frequency of KRAS in metastatic colorectal cancer: A retrospective analysis of a cancer center in Brazil
Approximately half of metastatic colorectal cancers (mCRC) have somatic KRAS mutations. Such mutations confer a worse prognosis in relation to mCRC without KRAS mutations, and also predict lack of response to anti-EGFR therapy. Data on the prognostic value of KRAS allele frequency in mCRC are scarce. The present study aims to analyse the prognosis of KRAS mutations, in relation to the corresponding exon and their allele frequency, in patients with KRAS-mutated mCRC.
A sum of 538 patients with mCRC (adenocarcinoma) were followed up at A.C. Camargo Cancer Center from February 2015 to June 2020. For the final analysis, 253 patients with KRAS-mutated mCRC were included, assayed by next-generation sequencing in tumor tissue. Patients with mCRC with NRAS or BRAF mutations, or without KRAS, NRAS or BRAF mutations, were excluded. A threshold of < 10% was admitted for low allele frequency.
Mutations in exon 2 were more frequent (N = 227), followed by mutations in exon 4 (N = 18) and exon 3 (N = 8). Patients with mCRC with KRAS mutations in exons 3 and 4 had a lower number of sites of metastasis at diagnosis; despite this, these patients had a lower overall survival (OS) compared to patients with exon 2 mutations (median OS 10.8 months [exon 3] versus 19.5 months [exon 4] versus 29.6 months [exon 2 ], P = 0.03). Analysis of OS in relation to allele frequency ( < 10% v ≥10%) was not statistically significant (P = 0.55).
The allele frequency of KRAS mutations in mCRC, assuming a threshold of < 10% for low allele frequency, had no prognostic impact in terms of OS. The study suggests that KRAS mutations in exons 3 and 4 have a negative impact in terms of OS in mCRC.
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All authors have declared no conflicts of interest.
