Prevalence and type of KRAS mutations in endometrial endometrioid carcinoma
Keywords:
Endometrioid carcinoma, KRAS, mutation, double mutationAbstract
Background: KRAS encodes a small G-protein that involves cell proliferation, differentiation, and survival.
Objectives: To determine the prevalence and type of KRAS mutations in Southern Thai patients with endometrial endometrioid carcinoma as well as their correlation with clinicopathological variables.
Methods: A total of 190 patients with endometrioid carcinoma were analyzed for KRAS exon 2 mutations using direct sequencing. The statistical correlation of KRAS mutations with clinicopathogical variables was also evaluated using the Chi-square or Fisher exact test.
Results: KRAS mutations were detected in 17.4% (33/190) of cases. All of them were missense mutations and 72.7% (24/33) occurred in hotspot codons 12 and 13. Of these mutations, 30 tumors presented as single mutations including; 16 mutations in codon 12 (p.G12C, p.G12D, p.G12S, and p.G12V), 5 mutations in codon 13 (p.G13C, and p.G13D), and 9 rare mutations in the flanking regions of the hotspot (p.E3K, p.E3G, p.V14I, p.G15S, p.H27Y, p.D30N, p.D33G, and p.P34S). Additionally, 3 tumors presented as double mutations in codon 12 as well as in codons 2, 6, and 7 (p.G12D and p.T2I, p.G12C and p.F6L, and p.G12D and p.E7M). KRAS mutations were often found in patients with histologic grades 1 and 2 and FIGO stages I. There was a significant relationships between the presence of KRAS mutations and FIGO staging (P = 0.041), but no any mutations were significant correlated with other clinicopathological variables such as body mass index, myometrial invasion, LVSI, and synchronous ovarian cancer/ovarian metastasis.
Conclusion: This study suggests that the presence of KRAS mutations as single or double mutations would be a relatively common early event in endometrial carcinogenesis among this subgroup of Thai patients.
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