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Gastrointestinal Cancer

High Concordance of KRAS Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice

^aDepartment of Oncology and ^hSurgical Pathology, University Campus Bio-Medico, Rome, Italy; ^bDepartment of Oncology, Azienda USL6 Livorno, Istituto Toscano Tumori, Italy; ^cDepartment of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Pisa, Italy; ^dOncology Department, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; ^eDipartimento di Scienze Biomolecolari, University of Urbino, Urbino, Italy; ^fDivision of Medical Oncology, Azienda Ospedaliera San Salvatore, Pesaro, Italy; ^gSezione di Oncologia Medica, Dipartimento di Discipline Chirurugiche ed Oncologiche, and ⁱDipartimento di Patologia Umana, Università di Palermo, Palermo, Italy

Key Words. Colorectal cancer • KRAS mutations • Concordance • Metastatic sites • Primary tumors

Correspondence: Daniele Santini, M.D., Ph.D., Medical Oncology, University Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy. Telephone: 0039-06-225411206; Fax: 0039-06-225411934; e-mail: d.santini{at}unicampus.it

Received August 13, 2008; accepted for publication October 28, 2008; first published online in THE ONCOLOGIST Express on December 4, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

Purpose. Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concordance in terms of KRAS status between primaries and related metastases.

Patients and Methods. We analyzed KRAS codon 12 and 13 mutations from formalin-fixed sections of 107 CRC primaries and related metastases. Eight pairs were excluded from the analysis because of the low amount of tumor tissue in the available samples. The main characteristics were: 50 men, 49 women; median age at diagnosis, 71 years (range, 41–84). The metastatic sites analyzed were the liver in 80 patients (80.8%), lung in seven patients (7.1%), and other sites in 12 patients (12.1%).

Results. A KRAS mutation was found in 38 (38.4%) primary tumors and in 36 (36.4%) related metastases. The rate of concordance was 96.0% (95% confidence interval, 90.0%–98.9%). Discordance was observed in only four (4%) patients.

Conclusions. Our results indicate that the detection of KRAS mutations in either primary or metastatic tumors from patients with CRC is concordant and this assessment could be used to predict response to targeted therapies such as cetuximab and panitumumab.

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