Abstract
BackgroundThe aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing.MethodsAll incident CRC cases in 2010 were identified in the Poitou-Charentes General Cancer Registry. The exhaustive molecular testing performed was accessed in the French molecular genetics platform. Factors influencing prescription were analyzed using logistic regression.ResultsAmong the 1269 CRCs included in the study, KRAS, BRAF and MSI testing accounted for 35.1%, 10.5% and 10.9%, respectively. KRAS testing was carried out in 65.5% of metastatic CRCs, and 26.1% of non-metastatic CRCs. Among metastatic CRCs, age (<60 years), site of primary tumour (left colon) and geographical area of treatment were factors related to KRAS testing. BRAF testing was contemporary to KRAS testing for 92.5% of patients. Factors related to MSI testing were age (<60 years), TNM stage (stage IV) and geographical area of treatment. Among CRC patients under 60 years old, only 37.5% had MSI testing.ConclusionThese results underscore the need to reduce disparities in CRC molecular testing and highlight the limited application of the French guidelines, especially concerning MSI testing.
Highlights
The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing
KRAS was mutated in 41.7% of cases (n = 175/420), BRAF mutation in 24.2% (n = 31/128) and a DNA mismatch repair (dMMR) phenotype was found in 16.8% (n = 22/131)
Age at diagnosis, site of primary tumor, stage at diagnosis, geographical area of primary treatment and status of the center were the factors related to KRAS testing
Summary
The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing. MSI is related to a deficient DNA mismatch repair (dMMR) system due to germline mutation in a MMR gene in Lynch syndrome (LS), or more commonly to an epigenetic inactivation of MLH1 in sporadic cases. 45% of CRC cases have a KRAS mutation [2] and only patients with wild-type (WT) RAS metastatic CRC (mCRC) may benefit from anti-epidermal growth factor receptor monoclonal antibody therapy (anti-EGFR mAbs). A BRAF mutation (V600E) is present in approximately 12% of CRCs and confers a poor prognosis, especially in mCRCs [5–8]. In dMMR CRC, BRAF mutation is specific to a sporadic origin and eliminates a LS
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