European Journal of Epidemiology

, Volume 26, Issue 3, pp 229–236 | Cite as

Clinical validity of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients

  • Lucy A. Parker
  • Miquel Porta
  • Blanca Lumbreras
  • Tomàs López
  • Luisa Guarner
  • Ildefonso Hernández-Aguado
  • Alfredo Carrato
  • Josep M. Corominas
  • Juli Rifà
  • Esteve Fernandez
  • Joan Alguacil
  • Núria Malats
  • Francisco X. Real
CANCER
First Online:
Received:
Accepted:

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.

Keywords

KRAS oncogene Genes, ras Oncogene protein p21 ras Pancreatic neoplasms/diagnosis Research/methods Diagnosis/diagnostic use Diagnosis/analysis Diagnosis/methods Epidemiology/diagnosis 

Abbreviations

BPD

Benign pancreatic disease

CEBS

Cancer of the extra-hepatic biliary system

CI

Confidence interval

CP

Chronic pancreatitis

EPC

Exocrine pancreatic cancer

ERCP

Endoscopic retrograde cholangio-pancreatography

IQR

Interquartile range

OBD

Other benign disease

OM

Other malignancy

OR

Odds ratio

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Notes

Acknowledgments

Supported in part by research grants from the Government of Catalonia (2009 SGR 1350, CIRIT 1999 SGR 00241 and 1998/BEAi400011); CIBER de Epidemiología y Salud Pública (CIBERESP), ‘Red temática de investigación cooperativa de centros en cáncer’ (C03/10), ‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’ (C03/09), and Fondo de Investigación Sanitaria (91/595, 92/0007, 95/0017 and 97/1138), Instituto de Salud Carlos III, Madrid, Government of Spain. The authors gratefully acknowledge scientific and technical assistance provided by Antonio Salas, Montserrat Andreu, Josep Lluís Piñol, Angels Serrat, David J. MacFarlane, Laura Ruiz, Elisabeth Carrillo, José Pumarega, Marta Crous-Bou, Leo Español, Puri Barbas and Yolanda Rovira.

Conflict of interest

The authors declare they have no competing financial interests nor other conflicts of interest. The study sponsors had no role and no involvement in the study design, nor in the collection, analysis, and interpretation of data; they also had no role and no involvement in the writing of the report, nor in the decision to submit the paper for publication.

Supplementary material

10654_2011_9547_MOESM1_ESM.doc (394 kb)
Supplementary material 1 (DOC 393 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Lucy A. Parker
    • 1
    • 3
  • Miquel Porta
    • 4
    • 5
    • 2
  • Blanca Lumbreras
    • 1
    • 3
  • Tomàs López
    • 3
    • 4
  • Luisa Guarner
    • 5
    • 6
  • Ildefonso Hernández-Aguado
    • 1
    • 3
  • Alfredo Carrato
    • 7
  • Josep M. Corominas
    • 4
    • 5
  • Juli Rifà
    • 8
  • Esteve Fernandez
    • 4
    • 9
  • Joan Alguacil
    • 4
    • 10
  • Núria Malats
    • 4
    • 11
  • Francisco X. Real
    • 4
    • 11
    • 12
  1. 1.Department of Public HealthMiguel Hernández UniversityAlicanteSpain
  2. 2.IMIM, UAB, CIBER en Epidemiología y Salud PúblicaBarcelonaSpain
  3. 3.CIBER en Epidemiología y Salud Pública (CIBERESP)BarcelonaSpain
  4. 4.Institut Municipal d’Investigació Mèdica (IMIM)Hospital del MarBarcelonaSpain
  5. 5.Facultat de MedicinaUniversitat Autònoma de BarcelonaCataloniaSpain
  6. 6.Hospital Vall d’HebronBarcelonaSpain
  7. 7.Hospital Ramón y CajalMadridSpain
  8. 8.Hospital Son DuretaPalma de MallorcaSpain
  9. 9.Catalan Institute of Oncology (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL)University of BarcelonaBarcelonaSpain
  10. 10.Universidad de HuelvaHuelvaSpain
  11. 11.Centro Nacional de Investigaciones OncológicasMadridSpain
  12. 12.Universitat Pompeu FabraBarcelonaSpain

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