KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

Abstract

Background:KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.Methods:Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.Results:KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.Conclusion:We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6–98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0% 95% CI 0.7–4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Mutación del gen KRAS en el cáncer de colon y recto

“…Nuestros hallazgos muestran la presencia de mutación del gen KRAS en 42% de los cánceres de colon y recto, cifra muy similar a la reportada en los múltiples trabajos publicados en la literatura 32,33,41 . Un hecho similar se observa en relación a la distribución porcentual de los distintos tipos de mutaciones, con sobre 80% de mutaciones del codón 12 y aproximadamente 20% en el codón 13.…”

“…Al igual que en otras series no se observaron diferencias en la frecuencia de mutación de KRAS y género, localización (colon o recto) y edad de los pacientes, así como tumor primario o metástasis 33 . A pesar de observar una mayor frecuencia de mutaciones en pacientes menores de 50 años, esta diferencia no fue estadísticamente significativa.…”

“…En el cáncer colorrectal se ha encontrado mutación del gen KRAS entre 30 y 50% de los casos 28,32,33 . La actual terapia de algunos estadios avanzados de colon y recto incluyen el uso de anticuerpos monoclonales (panitumumab, cetuximab), capaces de bloquear la activación del EGFr [34][35][36] .…”

Prevalencia y características de mutaciones somáticas del gen KRAS en pacientes chilenos con cáncer colorectal

“…Ambos valores caen dentro del rango descrito en estudios realizados en América del Norte y Europa 2,4,[9][10][11][12]20,21 . Un estudio similar realizado recientemente en una cohorte de 109 pacientes chilenos con CCR reportó 42% de mutación en KRAS 18 , similar a 48% reportado por un estudio español realizado en una cohorte de 186 pacientes 22 .…”

Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

“…Finally, tumor heterogeneity, in which the presence of mutations or their relative proportions vary within different regions of the tumor, is a described but incompletely understood phenomenon that can confound the results of KRAS and BRAF mutation testing, as well as IHC results. [37][38][39][40][41][42][43][44] In cases in which tumor heterogeneity is present, false-negative results can occur due to sampling error.…”