Can Serum be Used for Analyzing the KRASMutation Status in Patients with Advanced Colorectal Cancer?
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Purpose KRASmutations have been used widely as prognostic or predictive marker in patients withadvanced colorectal cancer (CRC). However, it may be difficult to obtain a tumor tissue foranalyzing the status of KRAS mutation in large proportion of patients with advanceddisease. Materials and MethodsWe obtained pairs of tumor and serum samples from 65 patients with advanced CRC,between March 2008 and July 2011. KRAS mutation status from the tumor samples wasanalyzed by genomic polymerase chain reaction and direct sequence, and KRASmutationstatus from the serum samples was determined by a genomic polymerase chain reaction–restriction fragment length polymorphism assay. ResultsKRAS mutations were detected in the serum samples of 26 patients and in the tumorsamples of 31 patients. KRAS mutation status in the serum and tumor samples wasconsistent in 44 of the 65 pairs (67.7%). There was a significant correlation between themutations detected in the serum sample and the mutations detected in the matched tumorsample (correlation index, 0.35; p < 0.004). Twenty-two of the 57 patients (38.5%) receivedanti-epidermal growth factor receptor therapy as any line therapy. There was no significantdifference in the overall survival (OS) in accordance to the status of KRASmutations in boththe serum and tumor samples (p > 0.05). In a multivariate analysis, liver metastasis andno cytoreductive operation were independent prognostic factors for decreased OS. ConclusionThe serum sample might alternatively be used when it is difficult to obtain
Abstract
Purpose KRASmutations have been used widely as prognostic or predictive marker in patients withadvanced colorectal cancer (CRC). However, it may be difficult to obtain a tumor tissue foranalyzing the status of KRAS mutation in large proportion of patients with advanceddisease. Materials and MethodsWe obtained pairs of tumor and serum samples from 65 patients with advanced CRC,between March 2008 and July 2011. KRAS mutation status from the tumor samples wasanalyzed by genomic polymerase chain reaction and direct sequence, and KRASmutationstatus from the serum samples was determined by a genomic polymerase chain reaction–restriction fragment length polymorphism assay. ResultsKRAS mutations were detected in the serum samples of 26 patients and in the tumorsamples of 31 patients. KRAS mutation status in the serum and tumor samples wasconsistent in 44 of the 65 pairs (67.7%). There was a significant correlation between themutations detected in the serum sample and the mutations detected in the matched tumorsample (correlation index, 0.35; p < 0.004). Twenty-two of the 57 patients (38.5%) receivedanti-epidermal growth factor receptor therapy as any line therapy. There was no significantdifference in the overall survival (OS) in accordance to the status of KRASmutations in boththe serum and tumor samples (p > 0.05). In a multivariate analysis, liver metastasis andno cytoreductive operation were independent prognostic factors for decreased OS. ConclusionThe serum sample might alternatively be used when it is difficult to obtain
참고문헌 (25)
- Parkin DM, "Global cancer statistics, 2002", CA Cancer J Clin, 55, pp.74~108 (2005)
- Jiang Y, "Assessment of K-ras mutation : a step toward personalized medicine for patients with colorectal cancer", Cancer, 115, pp.3609~3617 (2009)
- Andreyev HJ, "Kirsten ras mutations in patients with colorectal cancer : the 'RASCAL II' study", Br J Cancer, 85, pp.692~696 (2001)
- Bazan V, "Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype", Ann Oncol, 13, pp.1438~1446 (2002)
- Schubbert S, "Hyperactive Ras in developmental disorders and cancer", Nat Rev Cancer, 7, pp.295~308 (2007)
- Poehlmann A, "K-ras mutation detection in colorectal cancer using the pyrosequencing technique", Pathol Res Pract, 203, pp.489~497 (2007)
- Costa DB, "Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers", Lung Cancer, 58, pp.95~103 (2007)
- Schwarzenbach H, "Cell-free nucleic acids as biomarkers in cancer patients", Nat Rev Cancer, 11, pp.426~437 (2011)
- Gormally E, "Circulating free DNA in plasma or serum as biomarker of carcinogenesis : practical aspects and biological significance", Mutat Res, 635, pp.105~117 (2007)
- Kopreski MS, "Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer", Br J Cancer, 76, pp.1293~1299 (1997)
- Anker P, "K-ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer", Gastroenterology, 112, pp.1114~1120 (1997)
- Amado RG, "Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer", J Clin Oncol, 26, pp.1626~1634 (2008)
- Karapetis CS, "K-ras mutations and benefit from cetuximab in advanced colorectal cancer", N Engl J Med, 359, pp.1757~1765 (2008)
- Andreyev HJ, "Kirsten ras mutations in patients with colorectal cancer : the multicenter"RASCAL"study", J Natl Cancer Inst, 90, pp.675~684 (1998)
- Hurwitz H, "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer", N Engl J Med, 350, pp.2335~2342 (2004)
- Valent A, "Change in HER2(ERBB2)gene status after taxane-based chemotherapy for breast cancer : polyploidization can lead to diagnostic pitfalls with potential impact for clinical management", Cancer Genet, 206, pp.37~41 (2013)
- Dawson SJ, "Analysis of circulating tumor DNA to monitor metastatic breast cancer", N Engl J Med, 368, pp.1199~1209 (2013)
- Zlobec I, "Clinicopathological and protein characterization of BRAF-and K-RAS-mutated colorectal cancer and implications for prognosis", Int J Cancer, 127, pp.367~380 (2010)
- Naguib A, "Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study", BMC Cancer, 10, pp.99~ (2010)
- Gonzalez-Aguilera JJ, "Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer", Am J Clin Oncol, 27, pp.39~45 (2004)
- Westra JL, "Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients", J Clin Oncol, 23, pp.5635~5643 (2005)
- Leslie A, "Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas", Cancer Res, 63, pp.4656~4661 (2003)
- Baker SJ, "p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis", Cancer Res, 50, pp.7717~7722 (1990)
- Fearon ER, "A genetic model for colorectal tumorigenesis", Cell, 61, pp.759~767 (1990)
- Klein CA, "Parallel progression of primary tumours and metastases", Nat Rev Cancer, 9, pp.302~312 (2009)