KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Krieken, J.H.J.M. van; Jung, Andreas; Kirchner, Thomas; Carneiro, Fátima; Seruca, Raquel; Bosman, F.; Quirke, Philip; Fléjou, Jean‐François; Hansen, Tine Plato; Hertogh, Gert De; Jares, Pedro; Langner, Cord; Höefler, Gerald; Ligtenberg, Marjolijn J. L.; Tiniakos, Dina; Tejpar, Sabine; Bevilacqua, Generoso; Ensarı, Arzu

doi:10.1007/s00428-008-0665-y

Cited by 261 publications

(204 citation statements)

References 79 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…To date, results from this determination are heterogeneous and could be biased by many factors including: (1) selection of patients to test; (2) recovery of biological samples; (3) DNA extraction procedures; (4) choice of appropriate protocols for the determination of KRAS status, and (5) optimal reporting of test results. In May 2008, the European Society of Pathology in close collaboration with the European Quality Assurance Council proposed a European quality assurance program to establish guideline recommendations for accurately testing KRAS mutations [8]. …”

Section: Kras and Braf Mutations: Description And Detection Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

et al. 2009

View full text Add to dashboard Cite

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with metastatic colorectal carcinoma. Among patients not carrying activating mutations in the KRAS gene, only a limited number will experience tumor response to these therapeutic agents. The role of BRAF mutations in determining resistance to this treatment is emerging through preclinical and clinical studies. Standardization and validation of laboratory mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Clinical single-arm and randomized studies were conducted both in first-line and refractory settings to evaluate the correlation of KRAS mutational status and efficacy of cetuximab and panitumumab. The main trials on first-line regiments are CRYSTAL, which is looking at FOLFIRI (folinic acid, fluorouracil, irinotecan) + cetuximab, and OPUS, which is evaluating FOLFOX (folinic acid, fluorouracil, oxaliplatin) + cetuximab. The results of these trials have induced the European Medicines Agency to apply restrictions to its approval of cetuximab and panitumumab for use in metastatic colorectal cancer patients with wild-type KRAS tumors. However, the absence of KRAS mutations is not sufficient to assure clinical response to cetuximab and panitumumab. We need to discover further molecular biomarkers of impairment in this or other signaling pathways to identify responders more specifically. Preclinical rationale is available for combined therapies, which simultaneously target EGFR and the RAS/RAF/MAPK signaling pathways for metastatic colorectal cancer.

show abstract

Section: Kras and Braf Mutations: Description And Detection Methodsmentioning

confidence: 99%

“…This dimerization causes ATP-dependent phosphorylation of tyrosine kinase residues within the intracellular domain of the receptors. Tyrosine phosphorylation triggers activation of downstream signal transduction cascades which control cell growth, development, and function [7,8]. …”

Section: Biology Of the Kras/braf Pathwaymentioning

confidence: 99%

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In some reports, PCTDs were proposed to be vascular metastasis and that they are areas of vascular invasions [11,19,20]. In our cases, correlation between vascular invasion and PCTD presence was investigated and direct correlation was detected between PCTD and vascular invasion (r = 0.539, p = 0.0008).…”

Section: Discussionmentioning

confidence: 62%

“…In some studies, connection between K-ras mutation and resistance to EGFR inhibitors in metastatic CRCs were shown [13]. There are studies demonstrating that presence of codon 12 and 13 mutation in K-ras oncogene indicates poor response of patients to EGFR-targeted therapy [11].…”

Section: Discussionmentioning

confidence: 99%

“…CRC development is a result of acquisition of multiple genetic changes such as mutations of tumor suppressor genes and various prooncogenes. In recent studies, K-ras mutations were detected in rate of 30% -50% in colorectal adenocarcinomas [2][3][4][5][6][7][8][9][10][11][12]. K-ras gene is located on chromosome 12 and encodes G protein showing GTPase activity [2].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Frequency of K-ras Mutation in Colorectal Adenocarcinomas with Absence of Distant Metastasis at Diagnosis

Demıralay¹,

Saglam²,

Altaca³

et al. 2012

View full text Add to dashboard Cite

Purpose: K-ras mutations were reported to be in 40% -60% of patients with sporadic colorectal cancers (CRCs). HER-2/neu oncogene that is important in breast carcinoma was reported in CRCs in several studies. The aims of our study are to determine; the frequency of K-ras mutation in CRC and positivity of HER-2/neu, the relation between K-ras mutation and HER-2/neu positivity, and also the relation between clinicopathological findings with K-ras mutation and HER-2/neu expression. Methods: Total of 35 colon resection specimen from patients without distant metastasis who were operated due to colorectal adenocarcinoma were included in the study. The sections were examined with light microscopy. Vascular and perineural invasions and pericolonic tumor deposits (PCTD) were investigated. HER-2/neu was applied immunohistochemically. DNA sample obtained from tumor paraffin block was screened for presence of 20 mutations in K-ras gene-codon 12, 13, 61 by AutoGenomics and Infinity Analyzer. Results: K-ras gene mutation was detected in 14 of 35 patients (40%). HER-2/neu positivity was detected in 7 cases (28.57%). There was not any significant correlation between HER-2/neu positivity, K-ras gene mutation and clinicopathological findings. There was direct correlation between PCTD and vascular invasion. Conclusions: There was not correlation between K-ras mutation and clinicopathological findings similar to several other studies. The relation between HER-2/neu expression and clinicopathological findings was not found.

show abstract

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

et al. 2017

View full text Add to dashboard Cite

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

show abstract

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Cited by 261 publications

References 79 publications

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

The Frequency of K-ras Mutation in Colorectal Adenocarcinomas with Absence of Distant Metastasis at Diagnosis

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

Contact Info

Product

Resources

About