KRAS, NRAS, BRAF mutation comparison of endoscopic and surgically removed primary CRC paired samples: is endoscopy biopsy material adequate for molecular evaluation?

Abstract

Background:An everyday clinical practice dilemma in the 20–30% of metastatic colorectal cancer (CRC) patients that have not been operated on their primary tumour, is, under which specific histopathology and molecular circumstances, an endoscopic biopsy could be considered adequate to provide a representative RAS/BRAF molecular status to guide treatment.Methods:A consecutive series of 193 paired biopsy and primary CRC tumour samples between August 2008 and 2010 available in the Department of Pathology archives, University Hospitals, KU Leuven were retrieved. For a pair to be included, in the endoscopic biopsy, 20% of invasive adenocarcinoma cells should be present and enough slides to yield an extracted DNA concentration of ⩾5 ng μl−1, and no <2 ng μl−1 should be available for cutting. Exons 2–4 KRAS/NRAS, BRAF, PIK3CA molecular evaluation was performed with RT–PCR and Sequenom.Results:From 165 deemed adequate by the pathologist pairs, 85 (51.5%) were concordantly mutated in at least one of the tested genes, 70 (42.5%) were wt and 10 (6%) were discordant, harbouring a mutation in the primary and not in the endoscopic biopsy. In the re-evaluation, when more slides were cut per discordant pair, mutational status changed in two of the six discordantly KRAS-mutated pairs. A strong strength of agreement for both runs was observed (Cohen's kappa, k=0.877, P<0.001 and k=0.901, P<0.001, respectively) between the surgically acquired and the endoscopic biopsy specimens' evaluation.Conclusions:Based on our results, an endoscopic biopsy could provide an accurate mutational profile and become a justified alternative to a surgically removed primary tumour specimen, as long as specific histopathology criteria are met.

Prognostic factors of successful on-purpose tumor biopsies in metastatic cancer patients included in the SHIVA prospective clinical trial

“…Indeed, data of phase III TRIBUTE study showed that small samples were more likely to fail for molecular profiling with a failure rate of 55 to 65% in small samples (bronchoscopic transbronchial needle aspiration and CT-guided biopsy) compared with 24% in larger excisional biopsy or resection specimen [16]. In our study bronchoscopy showed the lowest results, according to literature [20]. The CT-guided biopsies had intermediate results with 67% of success, between surgery/palpation biopsy and endoscopic biopsies.…”

Treatment with checkpoint inhibitors in a metastatic colorectal cancer patient with molecular and immunohistochemical heterogeneity in MSI/dMMR status

“…Technical issues are extensively discussed in the literature [19]. There is a general agreement that biopsy samples could be a reliable alternative to primary tumours for RAS and BRAF mutational profiling [20]. Instead, regarding MSI status, poor data are available on sampling issues.…”

A Triptolide Loaded HER2-Targeted Nano-Drug Delivery System Significantly Suppressed the Proliferation of HER2-Positive and BRAF Mutant Colon Cancer

“… 16 , 17 It was proved that the patients with BRAF mutations, especially V600E mutations did not react with anti-HER2 treatment. 8 , 18 , 19 Therefore, the development of novel anti-HER2 therapeutic agents for CRC treatment is an urgent need.…”