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

Author:

Santini Daniele1,Loupakis Fotios23,Vincenzi Bruno1,Floriani Irene4,Stasi Irene2,Canestrari Emanuele5,Rulli Eliana4,Maltese Paolo Enrico2,Andreoni Francesca5,Masi Gianluca2,Graziano Francesco6,Baldi Giacomo Giulio2,Salvatore Lisa2,Russo Antonio7,Perrone Giuseppe8,Tommasino Maria Rosa9,Magnani Mauro5,Falcone Alfredo23,Tonini Giuseppe1,Ruzzo Annamaria5

Affiliation:

1. a Department of Oncology, University Campus Bio-Medico, Rome, Italy

2. b Department of Oncology, Azienda USL6 Livorno, Istituto Toscano Tumori, Italy

3. c Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Pisa, Italy

4. d Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

5. e Dipartimento di Scienze Biomolecolari, University of Urbino, Urbino, Italy

6. f Division of Medical Oncology, Azienda Ospedaliera San Salvatore, Pesaro, Italy

7. g Sezione di Oncologia Medica, Dipartimento di Discipline Chirurugiche ed Oncologiche, Università di Palermo, Palermo, Italy

8. h Surgical Pathology, University Campus Bio-Medico, Rome, Italy

9. i Dipartimento di Patologia Umana, Università di Palermo, Palermo, Italy

Abstract

Abstract 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. Learning Objectives After completing this course, the reader should be able to: Describe the importance of KRAS mutations in CRC patients.Explain the relevance to cancer treatment of concordance of KRAS status between primary tumors and metastases in CRC patients.Discuss the impact of KRAS mutations as a predictive/prognostic factor in CRC patients. CME This article is available for continuing medical education credit at http://CME.TheOncologist.com

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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