KRAS mutation status concordance between the primary tumor and the corresponding metastasis in patients with rectal cancer

Abstract

Introduction Oncogenic mutation within the KRAS gene represents a negative predictor for treatment response to anti-epidermal growth factor receptor (EGFR) in patients with colorectal cancer. Recently, we have shown no relevant heterogeneity for KRAS mutation status within and between pre-and posttherapeutic samples from the primary tumor in patients with locally advanced rectal cancer. The aim of this study was to evaluate the intertumoral heterogeneity of KRAS mutation status between the primary tumor and the corresponding metastasis or local recurrence in the similar cohort and to evaluate the ideal representative tissue for KRAS mutation testing. Materials and methods KRAS mutation status was analyzed from 47 patients with locally advanced rectal cancer, which were enrolled in the CAO/ARO/AIO-94 or CAO/ARO/AIO-04 trial. Mutations in KRAS codons 12, 13, and 61 were analyzed by using the KRAS RGQ PCR Kit (therascreen® KRAS test). Six patients needed to be excluded due to incomplete follow up data. 11 patients showed a relapse of the disease during the follow up presented by distant metastases or local recurrence. DNA from representative areas of metastatic tissue was obtained from formalin-fixed paraffin-embedded specimens. Results The mean patient age was 64.13 ± 10.64 years. In total, 19 patients showed a KRAS mutation (46.34%) in the primary tumor. Of the eleven patients with a metastatic disease or local recurrence, five patients showed a KRAS mutation whereas six patients had a KRAS wildtype status. Metastatic localizations included the liver (n = 2), lung (n = 4), local recurrence

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy

“…However, few studies have investigated the role of KRAS mutations in patients with LARC. Our results showed that KRAS mutations were present in 24.7% of patients, a lower frequency than reported in other publications [ 20 , 21 , 22 ]. In our study, we found that KRAS mutations were significantly associated with poorer OS and PFS in LARC patients receiving nCRT, but there was no relation between KRAS mutations and TRG.…”

Biological factors driving colorectal cancer metastasis

“…Subgroup analyses stratified by ethnicity showed that in Asian populations, KRAS, BRAF, and TP53 mutations, including lymph node and distant metastasis, were associated with mCRC, whereas only TP53 mutations promoted mCRC in Caucasians. Jo et al [ 11 ] investigated the difference between mCRC primary tumors and mCRC metastatic tissues and identified a significant concordance of KRAS mutation status in 81.18% (9/11) of patients ( P = 0.03271). Only two patients showed intertumor heterogeneity.…”

Which patients are prone to suffer liver metastasis? A review of risk factors of metachronous liver metastasis of colorectal cancer

“…RAS gene expression was consistent between CRC and metastatic lesion. Probably, occurrence of metachronous liver metastasis may be predicted by postoperative genetic mutations [ 114 ]. Nevertheless, specific location and pattern of tumor metastasis related to KRAS are always disputed.…”