Concordance of KRAS, NRAS and BRAF status between primary colorectal tumors and paired metastasis (mts)

Background

It is well established that patients with RAS-mutant colorectal cancer (CRC) are resistant to anti-EGFR therapies and it is suggested that BRAF mutations may also have a predictive value. However, it is not known which is the most suitable specimen for mutation testing. Although it has been postulated a high concordance of KRAS status between primary tumors (pt) and liver mts, there are contradictory results. In this study we investigated the concordance of KRAS, NRAS and BRAF between pt and matched hepatic and extrahepatic mts.

Methods

We examined 31 pairs of pt and mts (liver, lung, peritoneum, lymph nodes,ovary and pleura samples) of patients with CRC treated at Costa del Sol Hospital. DNA was extracted from formalin-fixed, paraffin-embedded specimens, using the DNA Tissue Kit (Qiagen). After verifying the quality of DNA, CLART CMA KRAS-BRAF Kit and Therascreen Kit or Therascreen KRAS RGQ PCR Kit, exon 15 BRAF sequencing and Therascreen Pyro Kit were employed to detect mutations in KRAS, NRAS and BRAF. To evaluate concordance differences, we used Fisher Test for independent cualitative variables, and U Mann-Whitney Test for cuantitative variables.

Results

Concordance rate of KRAS, NRAS and BRAF mutational status between pt and mts of any location was 79.1% (95% Confidence Interval: CI 65.7-92.4).

We found that discordant pairs of pt-liver mts for KRAS showed more frequently a percentage of tumor cells in pt samples

Conclusions

Concordance rate of approximately 80% can be found between pt and corresponding mts in unselected population of CRC patients. Percentage of tumor cells in samples can affect results. More studies are needed to clarify causes for discordance in mutational status of different samples from the same patient.

Clinical trial identification

Legal entity responsible for the study

Hospital Costa del Sol

Funding

Hospital Costa del Sol

Disclosure

All authors have declared no conflicts of interest.