Introduction The use of molecular markers as used biomarkers is steadily increasing routinely. amino-acid substitutions was noticed among KRAS codon 12 mutations. Components and Strategies We retrospectively evaluated data from 525 individuals who underwent a lung metastasectomy for CRC in two departments of thoracic medical procedures from 1998 to 2015 and centered on 150 individuals that got exon 2 codon 12/13 mutations. Conclusions KRAS exon 2 codon 13 mutations, in comparison to codon 12 mutations, appear to be connected with better results pursuing lung metastasectomy in CRC. Potential multicenter studies are essential to totally understand the prognostic worth of mutations in the lung metastases of CRC. ((mutations after lung metastasectomy of CRC, medical data are inconsistent [8C11] even now. Furthermore, clinical research on lung metastases of CRC appear to offer just a fleeting glance of the actual degree the molecular biology of tumor cells can offer inside our daily practice. Especially, the tumoral heterogeneity of mutations continues to be intriguing. Indeed, lately published data possess highlighted the lifestyle of two specific sets of cells: amino-acid substitution, different downstream signaling pathways are triggered [14], likely resulting in different medical behaviors such as for example different examples of aggressiveness [15], different Daphnetin manufacture sites of metastasis [16] and/or different sensitivity to chemotherapy radiation and [17] therapy18. Hence, few studies on metastatic CRC tried to evaluate the prognostic significance of KRAS codon 12 and codon 13 mutations, with contradictory results [19C22]. However, to the best of our knowledge, this axis has not been yet investigated in lung metastases of CRC. We thereby aimed to evaluate the different prognostic value of exon 2 codon 12 over codon 13 mutations in a large surgical cohort of resected lung metastases. RESULTS According to the selection criteria, 150 patients with lung metastasis of CRC harboring mutations were included in this study. The clinical-pathological characteristics of these patients are displayed in Table ?Table1.1. Median follow-up time was 56 months (IQR: 44). Table 1 Demographic data and main covariates according to KRAS mutational status Analyses of codon 12 transversions revealed 12 (8%) G12C, 39 (26%) G12V and 7 (5%) G12A. Analyses of codon 12 transitions revealed 49 (33%) G12D and 9 (6%) G12S. For KRAS codon 13, 34 (23%) cases Daphnetin manufacture of G13D transition were observed. Clinicopathological variables and mutations Table ?Table11 shows the Daphnetin manufacture distribution of clinicopathologic variables according to codon mutation. Survival analyses Ninety-five patients (63%) were reported to be alive, and 55 patients (37%) were dead during the follow-up period. Overall, the five-year survival rate was 42%. Survival analysis by codon mutation showed a non-significant difference between codon 12 and codon 13 mutations (median OS (mOS): 84 months vs 82 months, respectively; = 0.167). However, bevacizumab showed a survival benefit when used in case of codon 12 mutations (mOS: Not reached (NR) vs 54 months, < 0.001), but not in codon 13 mutations (mOS: NR vs 82 months; = 0.48). Patients were then further analyzed with the exclusion of patients treated with bevacizumab. Hence, survival analysis in patients not treated with bevacizumab showed a significant difference between codon 12 and codon 13 mutations (mOS: 54 months vs 82 months, respectively; = 0.009 - Figure ?Figure1).1). Otherwise, because among codon 12 mutations, G12D and G12V were Daphnetin manufacture the most frequent, other codon 12 mutations were pooled in the other codon 12 mutations group. There was no significant difference in mOS among codon 12 mutations (mOS: G12D 55, months (95% CI: 47.8C62) vs G12V, 55 months (95% CI 38.63C71.38) vs other codon 12 mutations, 53 months (95% CI 36.29C69.71); = 0.78). Figure 1 Kaplan-meier overall survival according to codon 12 or 13 mutations in patients not treated with bevacizumab Because Food and Drug Administration approval of FOLFOX YWHAS and bevacizumab in CRC were both obtained in 2004, we decided to compare OS between patients who underwent a lung metastasectomy before and after.