Abstract

IntroductionThe utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC).ResultsKRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61–82.56) vs 56 months (95% CI: 68.71–127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93–59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17–0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14–1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations.Materials and MethodsWe retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations.ConclusionsKRASexon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Highlights

  • The utilization of molecular markers as routinely used biomarkers is steadily increasing

  • Multivariate analysis confirmed that codon mutations were associated with better outcomes (TTPR: hazard ratios (HR): 0.40, P = 0.033); overall survival (OS): HR: 0.39, P = 0.07)

  • No significant difference in OS (P = 0.78) or Time to pulmonary recurrence (TTPR) (P = 0.72) based on the type of amino-acid substitutions was observed among Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12 mutations

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Summary

Introduction

The utilization of molecular markers as routinely used biomarkers is steadily increasing. Recent meta-analyses have helped to define main clinical prognostic factors [7]; in the past few years, there has been an increased understanding of the molecular alterations in cancer cells, with the identification of oncogenic drivers, suggesting that clinical factors could be a reflection of only gene mutations. These observations support the perspective of a molecular classification of patients, which carries with it the possibility of a better selection process for good surgical candidates [8,9,10,11]

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