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.

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

“…Another strength of the study is the assessment of KRAS mutations in tumor tissue, which is known to yield better sensitivity than detection in serum (Brychta et al ; Parker et al ; Parker et al ; Takai et al ). However, polymerase chain reaction and restriction fragment length polymorphism analysis yield a lower sensitivity to detect KRAS mutations than more modern techniques as droplet digital PCR, high resolution melting analysis, or next‐generation sequencing (Schlitter et al ).…”

“…Controls, recruited during 1998–2001, were patients with diagnoses unrelated to the exposures of interest (Amaral et al ; Garcia‐Closas et al ). In the PANKRAS II study (Alguacil et al , ; Crous‐Bou ; Crous‐Bou et al ; Parker et al ; Porta et al , , , ; Soler et al ), subjects were recruited between 1992 and 1995 at five general hospitals in Eastern Spain, where 185 incident cases of PDAC were prospectively identified. All their diagnoses were reviewed by a panel of experts and by the study reference pathologists, blinded to the original diagnoses and to molecular results (Porta et al ; Soler et al ).…”

“…More than 97% of PDAC cases were interviewed face‐to‐face by trained monitors during hospital stay, close to the time of diagnosis. Interviews included questions about past clinical history, signs and symptoms of pancreatic cancer, occupation, diet and coffee, and alcohol and tobacco consumption (Crous‐Bou ; Crous‐Bou et al ; Parker et al ; Porta et al , ; Soler et al ). A structured form was used to collect clinicopathological information from medical records, including details on diagnostic procedures, semiology, tumor stage, laboratory results, and follow‐up (Crous‐Bou et al ; Parker et al ; Porta et al , ; Soler et al ).…”

Glycomic and Proteomic Profiling of Pancreatic Cyst Fluids Identifies Hyperfucosylated Lactosamines on the N-linked Glycans of Overexpressed Glycoproteins

“…Gene and protein biomarker systems for pancreatic cancer have been extensively investigated, as is evidenced by the list of potential biomarkers asserted in the review by Harsha et al (4), but most candidates that have been tested clinically have not proved to be reliable for distinguishing between benign and malignant lesions of the pancreas (5,6). In the further pursuit of alternative molecular markers, the patterns of glycosylation have been studied in sera of patients with pancreatic cancer using antibody-and lectin-based sensors (7,8).…”

A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

“…This retrospective study analyzed 338 serum samples from patients with PDAC ( n = 156) and other pancreatic diseases (OPD) ( n = 152) and normal pancreatic controls (NPC) ( n = 30) that were collected after local ethical approval and informed consent at five different hospitals in Spain (Hospital del Mar, Barcelona; Hospital Vall Hebron, Barcelona; Hospital Mútua de Terrassa, Terrassa; Hospital Son Dureta, Palma de Mallorca; Hospital General Universitario de Elche, Elche), as part of the PANKRAS-II Study [ 25 , 26 ] from 1992 to 1995 ( Table 1 ).…”