title: KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancer.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  DNA 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.
  
  
  RESULTS
  PNA-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).
  
  
  CONCLUSIONS
  KRAS 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.
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China. jmxu2003@yahoo.com.|Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, No. 8 Dong Da Avenue, FengTai District, Beijing, 100071, China. jmxu2003@yahoo.com.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Xu
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China. lxj1982@163.com.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China. gefj1981@163.com.
authors.forename: Fei-Jiao
authors.initials: FJ
authors.lastname: Ge
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China. lin100@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China. pretty.wang@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA. msharma@bsd.uchicago.edu.
authors.forename: Manish R
authors.initials: MR
authors.lastname: Sharma
authors.affiliation: Affiliated Hospital Pharmacology Laboratory for Cancer Research, Academy of Military Medical Sciences, Beijing, China. zyliu1961@sina.com.
authors.forename: Ze-Yuan
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: National Cancer Research Centre, Istituto Tumori G Paolo II, Bari, Italy. s.tommasi@oncologico.bari.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: National Cancer Research Centre, Istituto Tumori G Paolo II, Bari, Italy. paradiso@oncologico.bari.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013997:Time Factors; D018631:ras Proteins / Q000097:blood* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins