scholarly journals Association of KRAS mutation with tumor deposit status and overall survival of colorectal cancer

2020 ◽  
Vol 31 (7) ◽  
pp. 683-689 ◽  
Author(s):  
Meifang Zhang ◽  
Wenwei Hu ◽  
Kun Hu ◽  
Yong Lin ◽  
Zhaohui Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Tumor Deposit

scholarly journals Association of Kras mutation with tumor deposit status and overall survival of colorectal cancer

2019 ◽  
Author(s):  
Meifang Zhang ◽  
Wenwei Hu ◽  
Kun Hu ◽  
Yong Lin ◽  
Zhaohui Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Cox Regression ◽  
Tumor Grade ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Kras Status ◽  
Tumor Deposit ◽  
Negative Tumor

AbstractBackgroundThe recent staging manual upstages Node-negative tumor-deposit positive colorectal cancer (CRC) from N0 to N1c category, while the development of tumor-deposit presence is poorly understood. Meanwhile, Kras mutation is associated with progression of CRC, but its link to tumor-deposit status is unclear.MethodThis retrospective cohort study included the patients with incidental CRC diagnosed during 2010-2014 in the National Cancer Database and recorded statuses of Kras and tumor deposit. We conducted multivariable logistic regression and Cox regression analyses to investigate the factors associated with tumor-deposit status and overall-survival, respectively.ResultsA total of 48,200 CRC patients with Kras status were included in the study (25,407 [52.7%] men, 25,648[46.8%] <65 years old, 18 381 [38.1%] with Kras mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, Kras mutation (versus wild-type) was associated with tumor-deposit presence (n=15,229, odds ratio=1.11, 95% CI 1.02 to 1.20). Kras mutation was also independently linked to a worse overall survival of CRC patients regardless of tumor-deposit status (n=8,110, adjusted Hazard ratio=1.40, 95% CI 1.09 to 1.79 for CRC with tumor deposits, and n=2,618, adjusted HR=1.63, 95% CI 1.16 to 2.28 for CRC without), but a better survival in CRC with no known/applicable tumor-deposit status (n=457, adjusted Hazard ratio =0.32, 95% CI 0.11 to 0.95).ConclusionKras mutation is independently associated with tumor-deposit presence, and a worse overall survival of CRC with or without tumor-deposit. Therefore, it may play a role in the development of tumor deposits and serve as a target for CRC treatment.

scholarly journals IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Renato Morato ZANATTO ◽  
Gianni SANTOS ◽  
Júnea Caris OLIVEIRA ◽  
Eduardo Marcucci PRACUCHO ◽  
Adauto José Ferreira NUNES ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Colorectal Carcinogenesis ◽  
Kras Mutations ◽  
Primary Tumor Site ◽  
Exon 2 ◽  
Metastatic Site ◽  
Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

BRAF and KRAS mutations as additional risk factors in the context of clinical parameters of patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3522-3522
Author(s):  
Vlad Calin Popovici ◽  
Eva Budinska ◽  
Arnaud Roth ◽  
Fred Bosman ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Tumor Site ◽  
Kras Mutations ◽  
P Values ◽  
Significance Level ◽  
Survival After Relapse

3522 Background: The BRAF and KRAS mutations have been proposed as prognostic markers in colorectal cancer (CRC). Of them, only the BRAF V600E mutation has been validated as prognostic for overall survival and survival after relapse, while the value of KRAS mutation is still unclear. Methods: In a cohort of 1423 stage II-III patients from the PETACC-3 clinical trial, the prognostic value of the BRAF and KRAS mutations was retrospectively assessed in all possible stratifications defined by the 5 factors (T and N stage, tumor site and grade, and microsatellite instability status), by log rank test for overall survival (OS), relapse-free survival (RFS), and survival after relapse (SAR). The presence of interactions was tested by Wald test. The significance level was set to 0.01 for Bonferroni-adjusted p-values (P*), and a second level for a trend towards statistical significance was set at 0.05 for unadjusted p-values (P). Results: BRAF mutation was a marker of poor OS only in microsatellite stable (MSS) and left-sided tumors, with no prognostic value in microsatellite instable (MSI-H) or right-sided tumors. In MSS/left-sided tumors, BRAF mutation represents a marker of higher risk than previously reported: OS HR=6.4 [95% CI: 3.6-11.5], P* < 0.0001. For SAR, BRAF was prognostic in more stratifications, with higher risk in MSS/left-sided tumors (HR=3.9 [95% CI: 2.1-7.2], P* = 0.0002) than in MSS/right-sided (HR=2.3 [95% CI: 1.2-4.4], P=0.01). A novel observation was that BRAF mutation was prognostic also for RFS, but only in MSS/left-sided tumors (HR=3.6 [95% CI:2-6.3], P*=0.0005]). Additionally, heterogeneity in OS and RFS among BRAF mutants was observed. In general, KRAS mutation did not reach the significance level required, but showed a trend to become a prognostic marker for RFS in MSS tumors with early lymph node involvement (N1) (HR=1.6 [95% CI:1.1-2.2], P=0.01). Conclusions: The prognostic utility of the BRAF and KRAS mutations has to be interpreted in the context of other factors. For the BRAF mutation, a clear interaction with MSI status and tumor site was observed, with BRAF mutation indicating a much higher risk in MSS/left-sided tumors than previously considered.

Predictive value of ERCC1 and KRAS in colorectal cancer patients with FOLFOX chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 588-588
Author(s):  
In Kyu Lee ◽  
Sung-Bong Choi ◽  
DaeYoung Cheung ◽  
Jin Il Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Disease Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference ◽  
Colorectal Cancer Patients ◽  
Disease Free

588 Background: To determine the clinical significance of KRAS mutation and ERCC1 overexpression as a predictive factor of resistance in oxaliplatin based treatment. Methods: We retrospectively analyzed the clinicopathologic features, status of KRAS mutation and ERCC1 overexpression of 386 colorectal cancer patients who received curative intent surgery. Among them 84 patients were treated by FOLFOX regimen as the first line. Their disease-free survival and overall survival according to the KRAS and ERCC1 were analyzed. Results: About a quarter of patients (25.5%) were represented KRAS wild type with ERCC1 overexpression. Among the patients who treated by FOLFOX regimen, 73 patients were evaluated both of the KRAS and ERCC1. There were no significant differences of disease-free survival and overall survival according to KRAS status and ERCC1 expression each. Under the subgroup analysis, overall survival of ERCC1 overexpression group in wild type KRAS was poor than ERCC1 negative group (p=.029), but no significant difference was in mutant KRAS group (p=.671). Conclusions: Our results suggest that the KRAS wild type with ERCC1 overexpression would be associated with the resistance of oxaliplatin.If oxaliplatin based chemotherapy would beconsidered, status of KRAS mutation and ERCC1 overexpression should be evaluated.

scholarly journals Clinical characteristics and prognostic value of the KRAS mutation in Chinese colorectal cancer patients

2021 ◽  
pp. 172460082110171
Author(s):  
Ye Yuan ◽  
Yingting Liu ◽  
Ye Wu ◽  
Junling Zhang ◽  
Chunti Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
High Frequency ◽  
Kras Mutation ◽  
Chinese Patients ◽  
Wild Type ◽  
Kras Mutations ◽  
Exon 2 ◽  
Colorectal Cancer Patients

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis. Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients. Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

Evaluation of BRAF mutation as a powerful prognostic factor in advanced and recurrent colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 413-413
Author(s):  
T. Yokota ◽  
T. Ura ◽  
N. Shibata ◽  
D. Takahari ◽  
K. Shitara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Clinicopathological Features ◽  
Wild Type ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Braf Mutant

413 Background: Alterations in the RAS/RAF/ERK signaling pathways frequently occur in colorectal cancer (CRC). KRAS mutations preclude responsiveness to EGFR-targeted therapies for CRC patients. However, prognostic significance of KRAS mutation is still controversial. The aim of this study is to investigate clinicopathological features of KRAS mutation in codon 12 and 13 as well as of BRAF mutation, and to validate prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC. Methods: The population consisted of 230 unselected patients who had undergone first-line chemotherapy for advanced and recurrent CRC between November 2002 and June 2010. Cycleave PCR was performed to detect a point mutation at codon 12, 13 or 61 in KRAS, and the V600E mutation in BRAF. Prognostic factors associated with survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. Results: KRAS mutations were present in 34.8% (n= 80) of patients, including 23.5% (n = 54) in codon 12, 11.3% (n = 26) in codon 13, and 0% in codon 61. 6.5% (n = 15) of patients had BRAF mutation. None of the CRC patients carried both KRAS and BRAF mutations. The primary tumor lesions were located on the right side of the colon in 60% of the BRAF mutant patients (p=0.0371). Furthermore, BRAF mutant was significantly associated with the pathological subtypes of poorly differentiated adenocarcinoma/mucinous carcinoma (p<0.0001) and peritoneal metastasis (p=0.0059). The median overall survival for BRAF mutant and KRAS 13 mutant patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for KRAS wild-type (wt)/BRAF wt (40.6 months) (BRAF; HR=3.89, 95% CI 1.83-8.24, p<0.001, KRAS13; HR=2.03, 95% CI 1.10-3.74, p=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor overall survival (HR, 3.70, 95% CI, 1.48-9.28; p=0.005), together with performance status 2. Conclusions: This retrospective analysis shows that clinicopathological features of CRC patients with BRAF mutations seem to be distinct from those with wild type BRAF. BRAF mutation is one of the most powerful prognostic factors in advanced and recurrent CRC. No significant financial relationships to disclose.

Prognostic value of DNA mismatch repair status and KRAS mutations in Korean colorectal cancer patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 697-697
Author(s):  
Soon Woo Hwang ◽  
Young-Seok Cho ◽  
Kim Kyeong Ok ◽  
Jae Myung Cha ◽  
Young-Eun Joo
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Mismatch Repair ◽  
Kras Mutation ◽  
Dna Mismatch Repair ◽  
Exon 2 ◽  
Dna Mismatch ◽  
Group 4 ◽  
Group 2

697 Background: The association of DNA mismatch repair (MMR) and KRAS mutation on clinical outcome of patients with colorectal cancer are frequently documented. However, development of more accurate prediction on clinical outcome using combination of both biomarkers remains a worthy area of investigation. The aim of this study was to evaluate the clinical relevance of KRAS mutation and MMR status in Korean patients with colorectal cancer (CRC). Methods: Clinical and pathological information for 1174 patients, who underwent surgery for colorectal cancer in 3 teaching hospitals from 2011 to 2013, were reviewed and recorded. Mutation analysis for exon 2 of KRAS gene was performed by Sanger sequencing. Expression of MMR proteins including MLH1 and MSH2 was evaluated by immunohistochemistry. Results: The overall frequencies of KRAS mutation was 34.9%. Mutations in KRAS codon 12 and codon 13 were detected in 26.7% and 8.2% of patients, respectively. Overall, 90 s (7.7%) tumors that had at least loss of expression for at least one MMR protein were defined as MMR protein deficient (MMR-D), and the remaining tumors were classified as MMR protein intact (MMR-I). According to KRAS mutation and MMR status, CRC was classified to 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group 4 had the best prognosis, and patients in Group 2 had the worst overall survival. KRAS mutation was independently associated with shorter time to recurrence and poorer overall survival. Conclusions: Combination status of KRAS mutation and MMR provide fundamental genetic signatures affecting tumor behavior, and may be used as a prognostic biomarker for CRC patient. These findings should be validated by further larger prospective study. [Table: see text]

KRAS mutation and microsatellite instability in colorectal cancer: Screening pattern and mutational landscape across the US.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15138-e15138
Author(s):  
Johannes Uhlig ◽  
Stacey Stein ◽  
Jill Lacy ◽  
Hyun S. Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Propensity Score ◽  
Microsatellite Instability ◽  
Kras Mutation ◽  
Locally Advanced ◽  
Matched Cohort ◽  
Middle Atlantic ◽  
Mutational Screening ◽  
The Us

e15138 Background: To assess screening patterns for KRAS mutation and microsatellite instability (MSI), associated mutational prevalence in colorectal cancer (CRC), and whether mutational screening affects survival. Methods: Patients with adenocarcinoma of the colon, sigmoid, and rectum were included from the 2010-2015 National Cancer Database. Socioeconomic, geographic and cancer factors were correlated with screening patterns. Propensity score matching was used to account for confounding. Overall survival was assessed in the matched cohort via Cox proportional hazards models. Results: 371,669 patients were included, of which 113,197 (30.4%) were screened: n=63,967 for MSI, n=33,319 for KRAS, and n=15,911 for MSI + KRAS. Younger patients with private insurance, high income locally advanced and metastatic sigmoid CRC treated at academic centers in Middle Atlantic and New England states were more likely to be screened. MSI was more prevalent among older female Caucasians from East South Central and Middle Atlantic States. KRAS mutation showed no significant discrepancies according to patient age or US geography, but was more prevalent among female African Americans. KRAS mutation was associated with locally advanced and metastatic CRC. MSI was more common in localized, non-metastatic CRC. Distinct mutational patterns were evident among primary CRC sites, with highest mutation rates in cecum/appendix and ascending colon (table). In the propensity score matched cohort with balanced distribution of confounders (n=157,678), mutational screening was not associated with overall survival (HR=1.012, 95% CI: 0.99-1.03, p=0.15). MSI versus MSS did not significantly influence patients´ overall survival (matched cohort n=26,014, HR=1.00, 95% CI: 0.96-1.05, p=0.88). Kras mutation versus wildtype showed decreased overall survival after accounting for confounders (matched cohort n=28,084, HR=1.11, 95% CI: 1.07-1.15, p<0.001). Conclusions: Testing for MSI and Kras mutation in CRC shows distinct patterns across the US, but does not influence outcomes. Decreased overall survival is observed in those patients with Kras mutation versus wildtype. [Table: see text]

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