19 Diagnostic Value of K-ras Mutations in Serum of Pancreatic Cancer Patients LIVIA THEODOR, a EHUD MELZER, MICHAEL SOLOGOV, AND SIMON BAR-MEIR Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel BACKGROUND AND AIMS The diagnosis of pancreatic carcinoma is sometimes difficult. Distinguishing pancreatic carcinoma from chronic pancreatitis is important and of obvious clinical implication. However, in some patients, neither the vague clinical presentation nor the current imaging modalities have clear-cut distinctive features. 1,2 A variety of tumor markers have been tested in the diagnostic workup of a pancreatic lesion, yet none has been proven as the ultimate one. 3,4 Therefore, an accurate and readily ac- cessible test to differentiate pancreatic cancer from chronic pancreatitis is highly warranted. K-ras oncogene is frequently mutated in pancreatic carcinomas, and several stud- ies have reported its presence in the pancreatic tissue of 75–95% of human pancre- atic adenocarcinoma. The mutation is at codon 12 of the K-ras oncogene and is considered as a critical and early event in pancreatic oncogenesis. 5–9 High rates of codon 12 K-ras mutations have been detected in DNA obtained by fine-needle aspiration from pancreatic masses, 10–14 as well as from duodenal or pure pancreatic juice 15–19 collected from patients with pancreatic cancer. However, K-ras mutations were also detected in a significant proportion of patients with chronic pancreati- tis, 20–24 markedly reducing the specificity of mutated K-ras gene as a potential tumor marker. A potential noninvasive source of DNA in pancreatic cancer patients is the serum. Circulating serum DNA levels were found to be elevated in patients with gastrointes- tinal malignancies and, in particular, in patients with pancreatic carcinoma. 25–27 In- deed, K-ras mutations were demonstrated in plasma from 3/3 patients with pancreatic cancer. 28 The aim of this study was to test the feasibility of using mutated K-ras gene from the serum as a potential tumor marker for detection of exocrine pancreatic carcino- ma. In addition, the diagnostic value of both CA19-9 and K-ras mutations in serum was further investigated. a Address for correspondence: Livia Theodor, Ph.D., Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel 52621. Voice: 972 3 530-3182; fax: 972 3 530-2913. gastro@netvision.net.il