Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Abstract

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Differential expression and bioinformatics analysis of exosome circRNAs in pancreatic ductal adenocarcinoma

“…As a result, 48 mRNAs were chosen to construct a prognostic model ( Table 2 ). The risk score = (Coef1 * expression level of mRNA1) + (Coef2 * expression level of mRNA2) + (Coef n * expression level of mRNA n), mRNA coefs were calculated from multivariate cox regression coefficients [20] . The independent forecast value of the prognostic risk model was evaluated by univariate cox regression analyses, the result indicated that risk score, age and grade had significant values ( Fig.…”

“…The correlation between overall survival (OS) and mRNA expression was identified using the univariate cox regression analysis with a criterion of p-value < 0.001. Multivariate cox regression analysis (stepwise regression method, p-value < 0.2) was used to determine the independent factors for prognosis prediction [20] . Founded on the results of multivariate cox regression, we established a prognostic model, and patients were divided into a low or a high-risk group according to the median level of risk scores.…”

The Impact of KRAS Mutational Status on Long-Term Survival following Liver Resection for Hilar Cholangiocarcinoma

“…As previously reported [ 17 , 18 , 19 , 20 ], KRAS mutation analysis was performed at the Anatomic Pathology Unit of our University Hospital. Tumoral tissue was identified in hematoxylin-and-eosin-stained sections of formalin-fixed, paraffin-embedded archival blocks.…”

“…All KRAS mutations found were pathogenic mutations. As previously described [ 17 , 18 , 19 , 20 ], KRAS codons 12, 13, 59, 61, 117 and 146 were amplified in one PCR. Thermal cycling conditions were: 95 °C for 12 min followed by 40 cycles of 95 °C for 10 s, 55 °C for 20 s and 72 °C for 20 s. PCR conditions were as follows: primer concentration 200 nmol L −1 , MgCl 2 concentration 2 mmol L−1; 30 ng of genomic DNA and 12.5 µL of Eppendorf Prime mastermix (Eppendorf, Milan, Italy) in a final reaction volume of 25 µL.…”

The impact of RAS mutation on the treatment strategy of colorectal cancer

“…Studies reported discordances ranging from 4 to 32% to 100% concordance [48][49][50][51][52][53][54][55]. An Italian team managed by Ardito analyzed KRAS status for both the primary tumor and completely resected liver metastases in 107 patients and found a discordance incidence of 15.9% [56]. The main characteristics of these studies are presented in table II below.…”