KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancerReportar como inadecuado

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Journal of Experimental and Clinical Cancer Research

, 33:104

First Online: 10 December 2014Received: 15 October 2014Accepted: 24 November 2014DOI: 10.1186-s13046-014-0104-7

Cite this article as: Xu, JM., Liu, XJ., Ge, FJ. et al. J Exp Clin Cancer Res 2014 33: 104. doi:10.1186-s13046-014-0104-7


BackgroundThe optimal laboratory assay for detecting KRAS mutations in different biospecimens from patients with metastatic colorectal cancer mCRC, and the clinical relevance of these gene alterations is still in question. We analyzed the prognostic–predictive relevance of KRAS status, determined in tumor and plasma DNA by two different assays, in a large mono-institutional series of mCRC patients.

MethodsDNA sequencing and peptide-nucleic-acid-mediated-polymerase chain reaction clamping PNA-PCR were used to determine KRAS status in 416 tumor and 242 matched plasma DNA samples from mCRC patients who received chemotherapy only. Relationships with outcomes were analyzed with respect to the different assays and tissue types.

ResultsPNA-PCR was significantly more sensitive in detecting KRAS mutations than sequencing 41% vs. 30%, p < 0.001. KRAS mutations were more frequent in tumor tissue than in plasma sequencing, 38% vs. 17%, p < 0.001; PNA-PCR, 47% vs. 31%, p < 0.001. Median OS was consistently shorter in KRAS-mutated patients than KRAS wild-type patients, independent from the assay and tissue tested; the largest difference was in plasma samples analyzed by PNA-PCR KRAS mutated vs. wild-type: 15.7 vs. 19.1 months, p = 0.009. No association was observed between KRAS status and other outcomes. When tumor and plasma results were considered together, median OS in patients categorized as tissue-plasma KRAS negative-negative, tissue-plasma KRAS discordant, and tissue-plasma KRAS positive-positive were 21.0, 16.9 and 15.4 months, respectively p = 0.008.

ConclusionsKRAS mutation status is of prognostic relevance in patients with mCRC. KRAS mutations in both tumor tissue and plasma are a strong prognostic marker for poor outcomes.

KeywordsKras Colorectal cancer Prognosis Electronic supplementary materialThe online version of this article doi:10.1186-s13046-014-0104-7 contains supplementary material, which is available to authorized users.

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Autor: Jian-Ming Xu - Xiao-Jing Liu - Fei-Jiao Ge - Li Lin - Yan Wang - Manish R Sharma - Ze-Yuan Liu - Stefania Tommasi - Angel


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