KRAS Mutations Testing in Colorectal Carcinoma Patients in Italy: From Guidelines to External Quality Assessment

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Nicola Normanno¹^,²^*, Carmine Pinto³, Francesca Castiglione⁴, Alberto Bardelli⁵, Marcello Gambacorta⁶, Gerardo Botti⁷, Oscar Nappi⁸, Salvatore Siena⁹, Fortunato Ciardiello¹⁰, GianLuigi Taddei⁴, Antonio Marchetti¹¹

1 Cell Biology and Biotherapy Unit, INT Fondazione “G. Pascale”, Naples, Italy, 2 Pharmacogenomic Laboratory, CROM – Centro Ricerche Oncologiche di Mercogliano, Avellino, Italy, 3 Medical Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy, 4 Department of Human Pathology and Oncology, University of Florence, Florence, Italy, 5 Institute for Cancer Research and Treatment, Università di Torino, Torino, Italy, 6 Division of Pathology, Ospedale Niguarda Ca' Granda, Milan, Italy, 7 Surgical Pathology Unit, INT Fondazione “G. Pascale”, Naples, Italy, 8 Surgical Pathology and Cytopathology, Antonio Cardarelli Hospital, Naples, Italy, 9 The Falck Division of Medical Oncology, Department of Oncology, Ospedale Niguarda Ca' Granda, Milano, Italy, 10 Medical Oncology, Department of Experimental and Clinical Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Naples, Italy, 11 Center of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy

Abstract Top

Background

Monoclonal antibodies directed against the epidermal growth factor receptor (EGFR) have been approved for the treatment of patients with metastatic colorectal carcinoma (mCRC) that do not carry KRAS mutations. Therefore, KRAS testing has become mandatory to chose the most appropriate therapy for these patients.

Methodology/Principal Findings

In order to guarantee the possibility for mCRC patients to receive an high quality KRAS testing in every Italian region, the Italian Association of Medical Oncology (AIOM) and the Italian Society of Pathology and Cytopathology -Italian division of the International Academy of Pathology (SIAPEC-IAP) started a program to improve KRAS testing. AIOM and SIAPEC identified a large panel of Italian medical oncologists, pathologists and molecular biologists that outlined guidelines for KRAS testing in mCRC patients. These guidelines include specific information on the target patient population, the biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%). The two centers were offered to participate to a second round and both centers failed again to pass.

Conclusions

The results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of Italian centers.

Citation: Normanno N, Pinto C, Castiglione F, Bardelli A, Gambacorta M, et al. (2011) KRAS Mutations
Testing in Colorectal Carcinoma Patients in Italy: From Guidelines to External Quality Assessment. PLoS ONE 6(12): e29146. doi:10.1371/journal.pone.0029146

Editor: Rakesh K. Srivastava, The University of Kansas Medical Center, United States of America

Received: September 14, 2011; Accepted: November 21, 2011; Published: December 21, 2011

Copyright: © 2011 Normanno et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The external quality assessment was funded by the Italian divisions of Merck and Amgen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The Italian Association of Medical Oncology and the Italian Society of Pathology received an unrestricted grant from the Italian divisions of Amgen and Merck that was used to pay the expenses of the program. No fee was given to the participants or the organizers of the program. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

* E-mail: nicnorm@yahoo.com

full-text:
PLoS ONE: KRAS Mutations Testing in Colorectal Carcinoma Patients in Italy: From Guidelines to External Quality Assessment