Applications and limitations of oncogene mutation testing in clinical cytopathology

Semin Diagn Pathol. 2013 Nov;30(4):284-97. doi: 10.1053/j.semdp.2013.11.008. Epub 2013 Nov 12.


In an increased number of settings, cytology represents the only source of sampling and it often substitutes histology as an independent diagnostic modality. Thus, DNA molecular targets to stratify patients for targeted therapy are often evaluated on cytology. In addition, DNA mutational tests may refine indeterminate thyroid and pancreas cytology. This review discusses the applications and limitations of DNA mutational testing on cytology. With respect to histology, most cytological samples have the advantages of a purer population of tumor cells, with low stromal component, a better preserved DNA, and assessing at the same time of sample collection cellular adequacy for DNA testing. However, since in vitro diagnostic tests are licensed only for paraffin-tissue, all mutational assays on cytology are "home brew," requiring a rigorous validation process. This should take into account not only the performance characteristics of the molecular assay but also features inherent to any given cytological samples, such as its source, preparation type, fixation and staining modalities, and the most effective tumor cell enrichment methods. This calls for a change of cytotechnologists and cytopathologists mentality to collect and process the cytological samples not only for microscopy but also to assess clinically relevant molecular markers.

Keywords: Aspiration; BRAF; Cytology; EGFR; KRAS; NRAS; PCR; c-KIT.

Publication types

  • Review

MeSH terms

  • Cytodiagnosis / methods*
  • DNA Mutational Analysis / methods*
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Oncogenes / genetics*
  • Specimen Handling / methods