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KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

Knijn N, Mekenkamp LJ, Klomp M, Vink-Börger ME, Tol J, Teerenstra S, Meijer JW, Tebar M, Riemersma S, van Krieken JH, Punt CJ, Nagtegaal ID - Br. J. Cancer (2011)

Bottom Line: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases.In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant.In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, HB 6500, The Netherlands.

ABSTRACT

Background: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.

Methods: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.

Results: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.

Conclusion: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

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Related in: MedlinePlus

Overall concordance of the KRAS mutation status between primary tumour and liver metastasis (A), discordance without clinical impact (B), and discordance with clinical impact (C). Abbreviations: WT, wild type; MT, mutation.
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fig1: Overall concordance of the KRAS mutation status between primary tumour and liver metastasis (A), discordance without clinical impact (B), and discordance with clinical impact (C). Abbreviations: WT, wild type; MT, mutation.

Mentions: In 294 patients (96.4% 95% CI 93.6–98.2%), the same KRAS mutation status was obtained from the primary tumour and the corresponding liver metastasis. In 11 patients (3.6% 95% CI 1.8–6.4%), of which 7 had synchronous metastases at diagnosis and 4 developed metachronous metastases, we found a discordance between primary tumours and metastases. Five patients had a KRAS mutation in the primary tumour and not in the liver metastasis. Only one patient had a wild-type status of the primary tumour, while the metastasis showed a KRAS mutation. In five patients, the primary tumours had different KRAS mutations compared with the metastases. One of these patients had two primary tumours. Both primary tumours had the same KRAS mutation (Gly13Asp), while the liver metastasis had a different KRAS mutation (Gly12Ser). In another patient, the primary tumour had a double mutation (Gly12Asp/Gly12Val) and the metastasis had a Gly12Asp mutation (Figure 1, Table 3). Taken together, the observed discordance was clinically relevant in only six patients (2.0% 95% CI 0.7–4.2%).


KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

Knijn N, Mekenkamp LJ, Klomp M, Vink-Börger ME, Tol J, Teerenstra S, Meijer JW, Tebar M, Riemersma S, van Krieken JH, Punt CJ, Nagtegaal ID - Br. J. Cancer (2011)

Overall concordance of the KRAS mutation status between primary tumour and liver metastasis (A), discordance without clinical impact (B), and discordance with clinical impact (C). Abbreviations: WT, wild type; MT, mutation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065268&req=5

fig1: Overall concordance of the KRAS mutation status between primary tumour and liver metastasis (A), discordance without clinical impact (B), and discordance with clinical impact (C). Abbreviations: WT, wild type; MT, mutation.
Mentions: In 294 patients (96.4% 95% CI 93.6–98.2%), the same KRAS mutation status was obtained from the primary tumour and the corresponding liver metastasis. In 11 patients (3.6% 95% CI 1.8–6.4%), of which 7 had synchronous metastases at diagnosis and 4 developed metachronous metastases, we found a discordance between primary tumours and metastases. Five patients had a KRAS mutation in the primary tumour and not in the liver metastasis. Only one patient had a wild-type status of the primary tumour, while the metastasis showed a KRAS mutation. In five patients, the primary tumours had different KRAS mutations compared with the metastases. One of these patients had two primary tumours. Both primary tumours had the same KRAS mutation (Gly13Asp), while the liver metastasis had a different KRAS mutation (Gly12Ser). In another patient, the primary tumour had a double mutation (Gly12Asp/Gly12Val) and the metastasis had a Gly12Asp mutation (Figure 1, Table 3). Taken together, the observed discordance was clinically relevant in only six patients (2.0% 95% CI 0.7–4.2%).

Bottom Line: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases.In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant.In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, HB 6500, The Netherlands.

ABSTRACT

Background: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.

Methods: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.

Results: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.

Conclusion: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Show MeSH
Related in: MedlinePlus