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Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status

Modest, Dominik P.a; Stintzing, Sebastiana; Laubender, Ruediger P.b; Neumann, Jensc; Jung, Andreasc; Giessen, Clemensa; Haas, Michaela; Aubele, Philippa; Schulz, Christopha; Boeck, Stefana; Stemmler, Hans-Joachima; Kirchner, Thomasc; Heinemann, Volkera

doi: 10.1097/CAD.0b013e3283493160

This retrospective study investigated the clinical characteristics of patients with metastatic colorectal cancer (mCRC) depending on the KRAS status, thereby differentiating KRAS exon 2 mutations in codon 12 versus codon 13. In total, 273 patients with mCRC receiving first-line therapy were analyzed. One hundred patients were treated within the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab), 147 patients within the AIO KRK-0104 trial (cetuximab plus CAPIRI or CAPOX), and further 26 patients received therapy outside the study. Thirty-eight tumors with KRAS mutation in codon 13, 140 tumors with mutation in codon 12, and 95 tumors with KRAS wild type as a comparison were included in this analysis. Bivariate analyses demonstrated significant differences between KRAS wild-type, codon 12-mutated, and codon 13-mutated tumors with regard to synchronous lymph node metastasis (P=0.018), organ metastasis (76.8% vs. 65.9% vs. 89.5%, P=0.009), liver metastasis (89.5% vs. 78.2% vs. 92.1%, P=0.025), lung metastasis (29.5% vs. 42.9% vs. 50%, P=0.041), liver-only metastasis (48.4% vs. 28.8% vs. 28.9%, P=0.006), and metastases in two or more organs (49.5, 61.4, 71.1, P=0.047). Regression models indicated a significant impact of KRAS mutations in codon 12 versus codon 13 for synchronous organ and nodal metastasis (P=0.01, 0.03). This pooled analysis indicates that mCRC is a heterogeneous disease, which seems to be defined by KRAS mutations of the tumor. Compared with KRAS codon 12 mutations, codon 13-mutated mCRC presents as a more aggressive disease frequently associated with local and distant metastases at first diagnosis.

aMedical Department III, Hospital of the University

bInstitute of Medical Informatics, Biometry, and Epidemiology

cInstitute of Pathology, University of Munich, Munich, Germany

Correspondence to Professor Dr Volker Heinemann, Department of Medical Oncology University of Munich, Klinikum Grosshadern, Munich, Germany Tel: +49 89 7095 2250; fax: +49 89 7095 2257; e-mail:

Dominik P. Modest and Sebastian Stintzing contributed equally to this study.

Received April 14, 2011

Accepted May 25, 2011

© 2011 Lippincott Williams & Wilkins, Inc.