Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer. Issue 1 (28th May 2014)

• Record Type: Journal Article
• Authors: Schirripa, Marta; Cremolini, Chiara; Loupakis, Fotios; Morvillo, Manfredi; Bergamo, Francesca; Zoratto, Federica; Salvatore, Lisa; Antoniotti, Carlotta; Marmorino, Federica; Sensi, Elisa; Lupi, Cristiana; Fontanini, Gabriella; Gregorio, Veronica De; Giannini, Riccardo; Basolo, Fulvio; Masi, Gianluca; Falcone, Alfredo
• Is Part Of: International journal of cancer. Volume 136:Issue 1(2015:Jan. 01)
• Page Start: 83
• Page End: 90
• Publication Date: 2014-05-28
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28955
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>NRAS</italic> mutations occur in 3–5% of colorectal cancer. Differently from <italic>KRAS</italic> and <italic>BRAF</italic> mutations, the role of <italic>NRAS</italic> mutations as prognostic and predictive markers in metastatic colorectal cancer (mCRC) has been investigated to a lesser extent. A retrospective series suggested the role of <italic>NRAS</italic> mutations as predictors of resistance to anti‐EGFR monoclonal antibodies (MoAbs) in chemo‐refractory patients with mCRC. In our study, <italic>KRAS</italic> codons 12, 13, 61 and <italic>BRAF</italic> codon 600 mutational status were evaluated in mCRCs referred to our Institution from 2009 to 2012. <italic>NRAS</italic> codons 12, 13 and 61 mutational status was analyzed in <italic>KRAS</italic>/<italic>BRAF</italic> wt patients. We collected pathological and clinical features in the overall population and outcome data in a subset of <italic>NRAS</italic> mutated chemo‐refractory patients treated with anti‐EGFR MoAbs in advanced lines. <italic>NRAS</italic> was mutated in 47/786 (6%) mCRCs. <italic>NRAS</italic> and <italic>KRAS</italic> mutated tumors did not show significant differences in terms of clinical and pathological characteristics, except for a lower prevalence of mucinous histology (<italic>p</italic> = 0.012) and lung metastases (<italic>p</italic> = 0.012) among <italic>NRAS</italic> mutated tumors. In the uni‐ and multivariate model, <italic>NRAS</italic> mutations were associated with shorter overall survival (OS) compared to all wt patients (median OS 25.6 <italic>vs</italic> 42.7 months; univ: HR = 1.91, 95% CI 1.39–3.86, <italic>p</italic> = 0.0013; multiv: HR = 1.75, 95% CI 1.1.3–2.72, <italic>p</italic> = 0.013). None of the chemo‐refractory <italic>NRAS</italic> mutated patients evaluable for response to anti‐EGFRs achieved response. In conclusion, <italic>NRAS</italic> mutations have a relevant incidence in patients with mCRC and showed an association with specific clinical and pathological features. <italic>NRAS</italic> mutations affect mCRC patients' prognosis and predict lack of response to anti‐EGFRs.</p> </abstract>