Implementation of formalin-fixed, paraffin-embedded cell line pellets as high-quality process controls in quality assessment programs for KRAS mutation analysis

J Mol Diagn. 2012 May-Jun;14(3):187-91. doi: 10.1016/j.jmoldx.2012.01.002. Epub 2012 Mar 10.

Abstract

In recent years, the mutational status of the KRAS oncogene has become incorporated into standard medical care as a predictive marker for therapeutic decisions related to patients with metastasized colorectal cancer. This is necessary, because these patients benefit from epidermal growth factor receptor (EGFR)-targeted therapy with increased progression-free survival only if the tumor does not carry a mutation in KRAS. Many different analytical platforms, both those commercially available and those developed in house, have been used within pathology laboratories to assess KRAS mutational status. For a testing laboratory to become accredited to perform such tests, it is essential that they perform reliability testing, but it has not previously been possible to perform this kind of testing on the complete workflow on a large scale without compromising reproducibility or the mimicry of the control sample. We assessed a novel synthetic control for formalin-fixed, paraffin-embedded (FFPE) tumor samples in a blind study conducted within nine laboratories across Europe. We show that FFPE material can, at least in part, mimic clinical samples and we demonstrate this control to be a valuable tool in the assessment of platforms used in testing for KRAS mutational status.

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • DNA Mutational Analysis / standards*
  • ErbB Receptors / antagonists & inhibitors
  • Fixatives
  • Formaldehyde
  • Genes, ras*
  • Humans
  • Molecular Diagnostic Techniques / standards*
  • Mutation
  • Paraffin Embedding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Quality Control
  • Reproducibility of Results
  • ras Proteins / genetics*

Substances

  • Fixatives
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Formaldehyde
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins