High Concordance of <i>KRAS</i> Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice

Santini, Daniele; Loupakis, Fotios; Vincenzi, Bruno; Floriani, Irene; Stasi, I.; Canestrari, Emanuele; Rulli, Eliana; Maltese, Paolo Enrico; Andreoni, Francesca; Masi, Gianluca; Graziano, Francesco; Baldi, Giacomo Giulio; Salvatore, Lisa; Russo, Antonio; Perrone, Giuseppe; Tommasino, Maria Rosa; Magnani, Mauro; Falcone, Alfredo; Tonini, Giuseppe; Ruzzo, Annamaria

doi:10.1634/theoncologist.2008-0181

Cited by 221 publications

(148 citation statements)

References 22 publications

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“…Ten of the tested pair samples (45.5%) had a wt-KRAS genotype and 12 of the tested pair samples (55.5%) were KRAS mutation positive. In contrast to EGFR expression which may differ in primary colorectal tumor tissue and the corresponding metastatic tissue, literature reports high concordance between KRAS mutations of primary and metastatic tumors from patients with colorectal carcinoma (31,32). This grade of concordance is important from two aspects.…”

Section: Discussionmentioning

confidence: 99%

“…This grade of concordance is important from two aspects. Firstly it suggests that KRAS mutations are an early event in colorectal carcinoma pathogenesis and are not essential for metastatic spread of the tumor (31). Secondly, if the primary tumor sample is not available, the evaluation of KRAS mutational status can also be performed from a metastatic site with relatively high confidence.…”

Section: Discussionmentioning

confidence: 99%

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KRAS mutations in Slovene patients with colorectal cancer: frequency, distribution and correlation with the response to treatment

Ličar

Cerkovnik²,

Ocvirk³

et al. 2010

Int J Oncol

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Abstract. KRAS mutations are proved as a predictor of response to EGFR-targeted therapies for patients with metastatic colorectal cancer. For identifying the wild-type KRAS (wt-KRAS) responder subset of patients who will benefit from novel agents our laboratory has introduced the TheraSreen K-RAS Mutation Kit ® an allele-specific RT-PCR based assay. Our aim is to describe the validation procedure of this method in our laboratory, determine the portion of colorectal cancer patients with wt-KRAS status, and assess the prognostic power of mutational status for the anti-EGFR therapy outcome in colorectal cancer patients. In this study 302 samples from 273 patients with metastatic colorectal cancer were tested for 7 most common mutations on codon 12 and 13 of the KRAS gene. We used HT-29 and CCL-247 cell lines to determine the sensitivity of the method for different proportions of tumor cells in the sample. We determined that 2% of cells carrying a KRAS mutation must be present in the sample for an undisputable detection of mutated signal using the LightCycler Adapt Software. Among the tested patients 54.5% had a wt-KRAS genotype and 45.5% had a mutated KRAS genotype. The p.Gly12Asp was the most common detected mutation (38.5%). Among the cetuximab therapy responders, 85.7% had a wt-KRAS genotype. We have shown that the RT-PCR method introduced to discriminate between anti-EGFR therapy responders and non-responders is efficient, reliable and quickly applicable. The ratio of mutated versus wt-KRAS patients in our study is similar to ratios reported by other authors, as is the high correlation between wt-KRAS genotype and response to cetuximab therapy. Nevertheless the selection of patients for treatment solely on the basis of KRAS status is not perfect due to the fact that some responders are among the patients with mutated KRAS and some non-responders among the wt-KRAS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

KRAS mutations in Slovene patients with colorectal cancer: frequency, distribution and correlation with the response to treatment

Ličar

Cerkovnik²,

Ocvirk³

et al. 2010

Int J Oncol

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“…However, only a minority of the studies reported in this review used techniques other than sequencing. Additionally, most studies on concordance have carefully reviewed the quality and tumor content of the samples included in their analysis, and some studies performed sequencing twice, starting from different amplification reactions [28,31,53], whereas others had two independent observers to determine KRAS status [50,52], or re-evaluated their results using pyrosequencing [54]. Therefore, although it is possible that a small number of the discordant cases are a result of poor quality testing techniques, false test results are not likely to explain the discordant cases in the majority of these studies.…”

Section: Discussionmentioning

confidence: 99%

Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review

et al. 2011

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Background. Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status is used as a decisional marker for epidermal growth factor receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients. Concordance of KRAS status between primary tumors and metastases has always been considered to be close to perfect; however, cases of discordance have been reported. The actual rate of concordance of KRAS status remains unclear, as is the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and tensin homologue deleted on chromosome ten (PTEN). Therefore, it is unknown whether it is necessary to perform mutational analysis on metastases instead of on (or in addition to) primary tumors.

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“…Recent experience in colorectal cancer has established that KRAS mutations in the primary tumor and the metastatic lesions are identical, 84,85 simplifying patient characterization for cetuximab treatment. Conversely, lung cancer studies have demonstrated substantial differences between primary and metastatic sites.…”

Section: Correlation Between Primary Tumor and Metastases Alterationsmentioning

confidence: 99%

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Ulivi

Calistri

Zoli

et al. 2010

J Nucleic Acids Invest

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In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma-or serum-derived DNA.

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High Concordance of KRAS Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice

Cited by 221 publications

References 22 publications

KRAS mutations in Slovene patients with colorectal cancer: frequency, distribution and correlation with the response to treatment

KRAS mutations in Slovene patients with colorectal cancer: frequency, distribution and correlation with the response to treatment

Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

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