Detection of somatic mutations of K-ras oncogene and allelic losses on chromosome 9p and 18q increase diagnostic significance of EUS-navigated fine needle biopsy in patients with focal pancreatic mass
Abstract
The aim of the study: Genetic methods enable more precious diagnosis of focal malignant pancreatic lesions. Many oncogenes and tumour supressor genes whose mutations are sequentially accumulated in the process of pancreatic oncogenesis were described.
The aim of the study is to optimalise the genetic test using DNA extracted from material from EUS-navigated fine needle biopsy (FNA). Material and methods: 81 patients suffering from pancreatic carcinoma and 20 patients with chronic pancreatitis were investigated by EUS-FNA.
The quality of FNA material was assessed by on-site cytologist during the investigation. DNA was extracted directly from cytology smears after laser micro-dissection of suspected cells.
Genetic analysis was directed to the mutations in K-ras and loss of heterozygosity on chromosome 9p and 18q where tumour supressor genes p16 nad DPC4 are located. Results: The test for presence of activating K-ras mutations revealed sensitivity and specificity 70 % and 100 %.
Detection of loss of heterozygosity revealed sensitivity and specificity 85 % and 64 % for locus 9p (p16), and 78 % and 57 % for locus 18q (DPC4) respectively. Combination of the tests for K-ras and allelic losses on locus 9p revealed sensitivity 92 % and specificity 64 %.
Conclusion: The highest sensitivity reveals genetic test which combines detection of point mutations in K-ras gene and loss of heterozygosity on locus 9p. This test is useful as a complementary test for malignancy in patients with focal pancreatic mass particularly when EUS-FNA was not able to distinguish between malignant and benign lesion (26 % of our material).