Aims The aim of our study was to analyse correlations between KRAS mutation status, chromosomal changes that affect KRAS status in cells from pancreatic tumours.
Methods We collected 69 cases of surgically resected pancreatic ductal adenocarcinoma (PDA) and seven cases of chronic pancreatitis (CP). Chromosomal abnormalities of KRAS and CEP12 were detected using fluorescence in situ hybridisation (FISH).
Results The number of CEP12 signals per cell ranged from 1.78 to 2.04 and 1.46 to 4.88 in CP and PDA samples, respectively, while the number of KRAS signals per cell ranged from 1.94 to 2.06 and 1.88 to 8.18 in CP and PDA samples, respectively. The ‘chromosomal instability index’, which was defined as the percentage of cells with any chromosomal abnormality, was over 5.7 times greater in PDA than in CP. We performed KRAS mutation analysis by direct sequencing and found that tumours with KRAS mutations have a significantly higher mean KRAS signal per cell from PDA samples compared with tumours with wild-type KRAS. KRAS amplification was noted in 10% of cases. Although we found that lymph node metastasis and distal metastasis of PDA were more frequent in cases with KRAS amplification, this was not correlated with overall survival. Using a threshold of 40%, we found that the chromosomal instability index robustly discriminated PDA cells from CP cells.
Conclusions Based on these findings, we concluded that FISH testing of KRAS using cytology samples may represent an accurate approach for the diagnosis of PDA.
- pancreatic cancer
- gene amplification
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Handling editor Runjan Chetty.
Contributors NS performed the experimental work, interpreted the data and drafted the manuscript. KA contributed to the experimental design and critically revised the manuscript. M Oda and M Orita contributed to data analysis and revisions of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Ethics approval Epidemiology Research Ethics Committee of Hiroshima University.
Provenance and peer review Not commissioned; externally peer reviewed.