Molecular markers for diagnostic cytology of neoplasms in the head region of the pancreas: Mutation of K-ras and overexpression of the p53 protein product

J. M. Van Es, M. M. Polak, F. M. Van den Berg, T. B. Ramsoekh, M. E. Craanen, R. H. Hruban, G. J.A. Offerhaus

Research output: Contribution to journalArticlepeer-review

Abstract

Aims - To determine the potential efficiency of molecular markers specific for neoplastic change - mutations of the K-ras oncogene and the p53 tumour suppressor gene - in diagnosing pancreatic carcinoma. Methods - Archival cytology samples obtained from 17 patients with established pancreatic carcinoma were assayed for alterations in K-ras and p53. To detect changes in p53 expression, immunocytochemistry with polyclonal antibody CM1 was performed on the archival cytology slides after destaining. Mutations in K-ras codon 12 were then analysed on the scrapings of the same slides using mutant enriched polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism analysis with allele specific oligonucleotide hybridisation for confirmation and characterisation. Results - False negative results were recorded for five of the cytology slides when compared with p53 immunostaining of the surgical resection specimen. These five cases had been stained previously with Giemsa which interacts adversely with the immunostaining in contrast to the Papanicolaou procedure. The K-ras codon 12 mutations followed the well distribution frequency and for pancreatic cancer and corresponded with the findings in the resection specimens in all cases. Two scrapings yielded insufficient DNA for PCR. Importantly, for two cases with an inconclusive cytology diagnosis on routine light microscopy, the diagnosis was confirmed by one of the molecular markers. The application of the molecular markers increased the diagnostic accuracy of cytology in this small study from 76 to 89%. Conclusions - The study indicates that assessment of alterations in the K-ras and p53 genes may be a valuable adjunct to diagnostic cytopathology of the head region of the pancreas, although there are some difficulties which will have to be overcome.

Original languageEnglish (US)
Pages (from-to)218-222
Number of pages5
JournalJournal of clinical pathology
Volume48
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Cancer
  • K-ras
  • Pancreatic
  • Polymerase chain reaction
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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