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

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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.

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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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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.

Author information

Authors and Affiliations

  1. Department of Public Health, Miguel Hernández University, Alicante, Spain

    Lucy A. Parker, Blanca Lumbreras & Ildefonso Hernández-Aguado

  2. IMIM, UAB, CIBER en Epidemiología y Salud Pública, Barcelona, Spain

    Miquel Porta

  3. CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    Lucy A. Parker, Blanca Lumbreras, Tomàs López & Ildefonso Hernández-Aguado

  4. Institut Municipal d’Investigació Mèdica (IMIM), Hospital del Mar, Barcelona, Spain

    Miquel Porta, Tomàs López, Josep M. Corominas, Esteve Fernandez, Joan Alguacil, Núria Malats & Francisco X. Real

  5. Facultat de Medicina, Universitat Autònoma de Barcelona, Catalonia, Spain

    Miquel Porta, Luisa Guarner & Josep M. Corominas

  6. Hospital Vall d’Hebron, Barcelona, Spain

    Luisa Guarner

  7. Hospital Ramón y Cajal, Madrid, Spain

    Alfredo Carrato

  8. Hospital Son Dureta, Palma de Mallorca, Spain

    Juli Rifà

  9. Catalan Institute of Oncology (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Barcelona, Spain

    Esteve Fernandez

  10. Universidad de Huelva, Huelva, Spain

    Joan Alguacil

  11. Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

    Núria Malats & Francisco X. Real

  12. Universitat Pompeu Fabra, Barcelona, Spain

    Francisco X. Real

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  1. Lucy A. Parker
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Correspondence to Miquel Porta.

Additional information

For the PANKRAS II Study Group: Members of the Multicentre Prospective Study on the Role of the K-ras and other Genetic Alterations in the Diagnosis, Prognosis and Etiology of Pancreatic and Biliary Diseases (PANKRAS II) Study Group are mentioned in previous publications.

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Parker, L.A., Porta, M., Lumbreras, B. et al. Clinical validity of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients. Eur J Epidemiol 26, 229–236 (2011). https://doi.org/10.1007/s10654-011-9547-8

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