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Published on: June 8, 2020
KRAS mutations testing in colorectal carcinoma patients in Italy: from guidelines to external quality assessment
Nicola Normanno1, Carmine Pinto, Francesca Castiglione
1Cell Biology and Biotherapy Unit, INT Fondazione G. Pascale, Naples, Italy. nicnorm@yahoo.com
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.
Insights
KRAS testing is crucial for metastatic colorectal carcinoma treatment. Italy
Area of Science:
- Oncology
- Molecular Diagnostics
- Gastroenterology
Background:
- EGFR-targeted monoclonal antibodies are approved for KRAS wild-type metastatic colorectal carcinoma (mCRC).
- KRAS mutation testing is mandatory for selecting appropriate mCRC therapy.
- Ensuring high-quality KRAS testing across all Italian regions is essential.
Purpose of the Study:
- To establish guidelines for KRAS testing in mCRC patients.
- To implement an external quality assessment program for KRAS testing in Italy.
- To evaluate the quality of KRAS mutational analysis in Italian centers.
Main Methods:
- AIOM and SIAPEC-IAP developed guidelines covering patient selection, sample handling, DNA extraction, and mutation analysis.
- An external quality assessment scheme involved sending five CRC specimens to 59 participating centers.
- Laboratories used their preferred methods and reported results within 4 weeks; a 100% accuracy rate was required to pass.
Main Results:
- Only 3% of centers (2 out of 59) failed the initial quality assessment.
- These two centers were re-evaluated in a second round and failed again.
- The majority of Italian centers demonstrated high-quality KRAS testing.
Conclusions:
- The first Italian quality assessment indicates that KRAS mutational analysis is performed with good quality in most centers.
- This program supports the reliable use of KRAS testing for mCRC treatment decisions in Italy.
