Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China

Li, Wenqi; Li, Huining; Liu, Ruiqi; Yang, Xinxin; Gao, Yuhui; Niu, Yangyang; Geng, Jiashi; Xue, Yingwei; Jin, Xiaoming; You, Qi; Geng, Jiao; Meng, Hongxue

doi:10.1159/000494649

Cited by 16 publications

(11 citation statements)

References 29 publications

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“…This study demonstrates that RAS and KRAS mutant status underline special clinicopathological and molecular features. As reported in some studies [15,28,29], in our context, RAS mutated CC was associated with female gender, distal colon, classical adenocarcinoma subtype, moderately differentiated tumors, and presence of vascular invasion. Interestingly, our study demonstrated that CC with RAS and epically KRAS mutations show a lower rate of the total lymph node.…”

Section: Discussionsupporting

confidence: 85%

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

et al. 2021

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This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.

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Section: Discussionsupporting

confidence: 85%

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

et al. 2021

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“…Some scholars have found that it is more common in women, 20 which is consistent with our results, but there are also literatures showing that there is no significant difference between men and women. 21 In addition, we found that the T stage of dMMR CRC is late, and the degree of tumor invasion is deep, consistent with the conclusions of other scholars. 22 Our research also showed that compared with patients with pMMR CRC, dMMR patients had a larger maximum tumor diameter and a higher percentage of tumors over 5 cm.…”

Section: Clinicopathological Characteristics Of Patients With Dmmrsupporting

confidence: 89%

Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

Yue

Cai

et al. 2021

OTT

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Purpose To investigate the clinicopathological characteristics of stage I–III colorectal cancer (CRC) patients with deficient mismatch repair (dMMR) protein. Patients and Methods A retrospective analysis of 61 patients with stage I–III CRC confirmed by immunohistochemistry as dMMR after radical resection at Shenjing Hospital of China Medical University from May 2017 to June 2019 was performed. A total of 183 stage I–III CRC patients with proficient mismatch repair (pMMR) protein from the same period were randomly selected as a control group. The clinicopathological data of the two groups were investigated. Results There were significant differences between the two groups in age, sex, site of onset, maximum diameter of tumor, T stage, tumor differentiation, and histological type ( P < 0.05). No significant difference was detected in nerve vessel invasion, cancer nodules, the N stage or the TNM stage. In the dMMR group, 41 patients (66.13%) showed PMS2/MLH1 deletion, and the number of MSH2/MSH6 deletion is 21 patients (33.87%). Among them, 34 patients (54.84%) had PMS2 and MLH1 deficiency. In total, 16 patients (25.81%) had MSH2 and MSH6 deficiency. A total of 5 patients (8.06%) showed simply PMS2 deletion and 5 patients (8.06%) showed simply MSH6 deletion. In total, 2 patients (3.23%) showed concurrent loss of PMS2, MLH1 and MSH2. No significant difference were found ( P > 0.05) in the above factors among dMMR CRC patients with different MMR proteins deletions. Conclusion Our results show that dMMR status may be more likely exist in female and younger (≤55 years) patients with a greater tumor burden (>5cm), right colon, T4 stage disease, poor differentiation and mucinous adenocarcinoma. Loss of PMS2 and MLH1 is the most common pattern of MMR protein expression deficiency, followed by concurrent deletion of MSH2 and MSH6.

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“…This is in the mid-range of reports from international series as shown in Table 4, where the proportion of RASmt was reported to range from less than 40% 12 up to 59%. 13 In our analyses, early data for both TRACC and TTT shows a RASmt rate around 40% and later data a RASmt rate around 50% in both databases. This increase largely coincides with the gradual uptake of extended RAS testing over several years, with further data on implication of RAS status on treatment, as well as easier access to EGFRi.…”

Section: Kras Mutation Only 470 (90%) E366 Discussionmentioning

confidence: 51%

“…The overall RASmt rate in our study of TRACC patients was 47% and for TTT was 45%. This is in the mid‐range of reports from international series as shown in Table 4, where the proportion of RASmt was reported to range from less than 40% 12 up to 59% 13 …”

Section: Discussionmentioning

confidence: 72%

Impact of the evolution in RAS mutation analysis in Australian patients with metastatic colorectal cancer

Chong

Jalali

Wong

et al. 2022

Asia-Pac J Clncl Oncology

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Background RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used. Aims To review routine care RAS testing and results over time. Methods A retrospective analysis of the molecular data collected prospectively in the multi‐site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011–2018. Results Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS mutant (RASmt). RAS data were available for 5935 TTT patients. Of the tested TRACC patients diagnosed in 2009 and 2010, 38% were RASmt. For each 2‐year period from 2011/2012 through to 2017/2018, the prevalence of RASmt in TRACC and TTT was 42% and 40% (2011/2012), 52% and 40% (2013/2014), 47% and 49% (2015/2016), and 47% and 49% (2017/2018). Conclusions Based on both TRACC and TTT data, the proportion of patients reported to have a RAS mutation increased from 2009 to 2015 but has remained relatively stable in recent years. The increased proportion of RASmt patients observed over time is likely largely driven by the uptake of extended RAS testing.

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Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China

Cited by 16 publications

References 29 publications

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

Impact of the evolution in RAS mutation analysis in Australian patients with metastatic colorectal cancer

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