Oncotarget

Research Papers:

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer

Stéphane Renaud _, Francesco Guerrera, Joseph Seitlinger, Lorena Costardi, Mickaël Schaeffer, Benoit Romain, Claudio Mossetti, Anne Claire-Voegeli, Pier Luigi Filosso, Michèle Legrain, Enrico Ruffini, Pierre-Emmanuel Falcoz, Alberto Oliaro and Gilbert Massard

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Oncotarget. 2017; 8:2514-2524. https://doi.org/10.18632/oncotarget.13697

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Abstract

Stéphane Renaud1,2,3, Francesco Guerrera1,4, Joseph Seitlinger1, Lorena Costardi4, Mickaël Schaeffer5, Benoit Romain3,6, Claudio Mossetti4, Anne Claire-Voegeli7, Pier Luigi Filosso4, Michèle Legrain7, Enrico Ruffini4, Pierre-Emmanuel Falcoz1, Alberto Oliaro4, Gilbert Massard1

1Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France

2Department of Thoracic Surgery, Nancy University Hospital, Nancy, France

3Research Unit EA3430, Tumoral Progression and Micro-Environment, Epidemiological and Translational Approaches, Strasbourg University, Strasbourg, France

4Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

5Department of Biostatistics, Strasbourg University Hospital, Strasbourg, France

6Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France

7Department of Molecular Biology, Strasbourg University Hospital, Strasbourg, France

Correspondence to:

Stéphane Renaud, email: [email protected]

Keywords: lung metastasectomy, colorectal cancer, KRAS, surgery, codon

Received: August 25, 2016     Accepted: November 21, 2016     Published: November 29, 2016

ABSTRACT

Introduction: The 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).

Results: KRAS 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 Methods: We 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.

Conclusions: KRAS exon 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.


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