Significance of K- ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer

Abstract

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K-ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K-ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K-ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P< 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K-ras mutation and CEA level in pancreatic juice, as well as serum CA19-9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K-ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.

Enrichment of Mutant KRAS Alleles in Pancreatic Juice by Subtractive Iterative Polymerase Chain Reaction

“…Base substitutions at the first or the second position of codon 12 were detected in each of the six carcinoma samples (Table 1). The finding of a KRAS mutation in one of nine samples from patients with chronic pancreatitis is not surprising because such mutations are also supposed to occur in nonmalignant lesions of the pancreas (Kimura et al, 1999). The siPCR results are based on the DNA sequence analysis as a definite method of confirming a specific base substitution.…”

“…Along with this detection method, the high fidelity of DNA amplification performed by a polymerase with proofreading activity (Pfu polymerase) supports the specificity of a siPCR assay. In a number of corresponding investigations, the mutant-enriched PCR has been applied (Kimura et al, 1999). DNA polymerases with proofreading activity cannot be used in this technique because the mismatch primers would be digested (Chen and Viola, 1991;Kahn et al, 1991).…”

Detection of K-ras point mutation and telomerase activity during endoscopic retrograde cholangiopancreatography in diagnosis of pancreatic cancer

“…K-ras gene mutation was found in greater than 90% of pancreatic cancers, and detection of K-ras gene mutation-positive cells in pure pancreatic juice or duodenal juice were reported to be useful in the diagnosis of pancreatic cancer [23][24][25][26] . K-ras mutation was detected in ERCP brush samples.…”

Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases

“…This diagnostic performance indicated that the K-ras mutation still remained the best marker of PC in pancreatic juice. However, several studies found K-ras codon 12 mutations in nonneoplasic pancreatic diseases or in normal pancreata [8,9,27,28], indicating these mutations lack specificity for PC diagnosis. A major concept emerging from the molecular analysis of human cancers is that cell progression to malignancy requires several hints: oncogene mutation and tumor suppressor gene inactivation.…”