title: Clinical validity of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients.
abstract: The diagnostic utility of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K-ras mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, pancreatic cysts, and cancer of the extrahepatic biliary system. Mutations in the K-ras oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K-ras mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K-ras or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K-ras and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K-ras mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K-ras analysis in conjunction with other genetic and 'omics' technologies.
authors.affiliation: Department of Public Health, Miguel Hernández University, Alicante, Spain.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Parker
authors.forename: Miquel
authors.initials: M
authors.lastname: Porta
authors.forename: Blanca
authors.initials: B
authors.lastname: Lumbreras
authors.forename: Tomàs
authors.initials: T
authors.lastname: López
authors.forename: Luisa
authors.initials: L
authors.lastname: Guarner
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Hernández-Aguado
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Josep M
authors.initials: JM
authors.lastname: Corominas
authors.forename: Juli
authors.initials: J
authors.lastname: Rifà
authors.forename: Esteve
authors.initials: E
authors.lastname: Fernandez
authors.forename: Joan
authors.initials: J
authors.lastname: Alguacil
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity