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Analysis of KRAS, BRAF, PTEN, IGF1R, EGFR intron 1 CA status in both primary tumors and paired metastases in determining benefit from cetuximab therapy in colon cancer

Cited 57 time in Web of Science Cited 59 time in Scopus
Authors
Park, Jin Hyun; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Jeong, Seung-Yong; Park, Kyu Joo; Kim, Tae-You; Bang, Yung-Jue; Park, Jae-Gahb
Issue Date
2011-10
Citation
Cancer Chemotherapy and Pharmacology, Vol.68 No.4, pp.1045-1055
Keywords
Colon cancerCetuximabKRASBRAFPTENEGFR intron 1 CA
Abstract
Purpose The aim of this study was to determine the expression of molecular markers in metastatic colorectal cancer (mCRC) and the concordance between primary tumor and metastasis. We also aimed to determine the relationship between molecular markers and clinical outcomes of cetuximab-containing chemotherapy. Methods Seventy-five mCRC patients who received cetuximab-containing chemotherapy between 2000 and 2008 were consecutively enrolled. EGFR, p-EGFR, PTEN, and IGF-1R expression by immunohistochemistry, DNA sequencing for EGFR, KRAS, BRAF, and PI3 KCA, and EGFR amplification by FISH were done. Results The positive expression of EGFR, p-EGFR, PTEN, and IGF-1R was determined in 45 (64.3%), 9 (14.8%), 35 (50.7%), and 10 patients (16.1%), respectively. EGFR gene amplification or high polysomy was detected in 10 patients (17.6%). KRAS mutation and BRAF mutation were detected in 19 patients (27.5%) and five patients (7.0%), respectively. Among tested biomarkers, only the EGFR intron 1 CA repeat polymorphism and BRAF mutation showed concordance (kappa = 0.600, P = 0.003; and kappa = 0.692, P = 0.001, respectively) between primary tumor and paired metastasis. Skin rash was a strong predictive marker for response rate, PFS, and OS. In KRAS mutant tumors, PTEN expression was associated with a longer PFS. BRAF mutation was related to poor outcome in KRAS wild-type tumors. Conclusions BRAF mutations and EGFR intron 1 CA repeat polymorphisms were concordant between primary tumors and paired metastases. In KRAS mutant tumors, PTEN expression was a predictive marker for favorable outcomes. In KRAS wild type, BRAF mutation was strong predictive markers for poor outcomes.
ISSN
0344-5704
URI
https://hdl.handle.net/10371/173016
DOI
https://doi.org/10.1007/s00280-011-1586-z
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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