KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis http://www.selleckchem.com/products/ldk378.html of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

British Journal of Cancer (2002) 87, 551�C554. doi:10.1038/sj.bjc.6600475 www.bjcancer.com ? 2002 Cancer Research UK Keywords: KRAS2 mutations, circulating DNA, pancreatic adenocarcinoma, chronic pancreatitis Five-year survival in patients with pancreatic adenocarcinomas is less than 5%, partly due to advanced disease at diagnosis. The differentiation between pancreatic cancer and chronic pancreatitis can be particularly difficult leading to inappropriate treatment. Serum carbohydrate antigen 19.9 (Ca 19.9) levels are elevated in 80% of pancreatic cancer patients, but can also be increased in 20% of patients with chronic pancreatitis (Satake and Takeuchi, 1994; Nouts et al, 1998).

Moreover, pancreatic inflammation, as observed in chronic pancreatitis, can be mistaken on imaging as cancer and inversely. An accurate and non-invasive test to differentiate pancreatic cancer from chronic pancreatitis would be extremely helpful. Previous studies have reported KRAS2 gene mutations (almost always confined to codon 12) in 75 to 95% of exocrine pancreatic cancer (Caldas and Kern, 1995). KRAS2 mutations provoke activation of nuclear transcriptor factors, resulting in cellular proliferation and also in tumour angiogenesis as reported recently (Banerjee et al, 2000; Ikeda et al, 2001). Detection of KRAS2 mutations were first reported in surgically removed pancreatic tumoural tissue or at autopsy (Almoguera et al, 1988; Tada et al, 1991).

Thereafter mutations were discovered in 63 to 83% of samples of pure pancreatic juice or main pancreatic duct brushing obtained during endoscopic retrograde pancreatography Batimastat (Iguchi et al, 1996; Kondo et al, 1997; Tada et al, 1998; van Laethem et al, 1998; Okai et al, 1999; Watanabe et al, 1999; Ha et al, 2001; Pugliese et al, 2001; Seki et al, 2001) or at fine-needle tumour aspiration (Pabst et al, 1999; Puig et al, 2000), and in 20 to 54% of stools (Caldas et al, 1994; Wenger et al, 1999) from patients with pancreatic cancer.