Serum tumor markers and molecular biological diagnosis in pancreatic cancer

Recent studies on genetic abnormalities in pancreatic ductal cancer have led to the investigation of tumor markers and genetic markers in both serum and pancreatic juice (PJ). Serum type 1 chain carbohydrate antigens such as CA19-9 are positive in nearly 80% of patients with pancreatic cancer (PCa), of which most are in advanced stage, whereas false-positive rates are relatively high at 20%-30% in benign hepatobiliary and pancreatic diseases. Although the prevalence of type 2 chain carbohydrate antigens, such as SLX, is relatively low, cancer specificity of these antigens is high. However, serum tumor markers have limited diagnostic value for early detection of PCa. In PJ collected endoscopically from patients with PCa, K-ras mutations (KRM) are detectable in > 80%, whereas KRM are observed in 20%-30% of PJ from patients with chronic pancreatitis (CP), reflecting benign mucous cell hyperplasia harboring KRM. Thus, a qualitative analysis of KRM in PJ is unsuitable for diagnosis of PCa. On the other hand, using an hybridization protection assay that can quantitatively determine KRM, KRM were positive in 66% of PCa but only in 40% of CP cases, indicating that qualitative analysis of KRM in PJ may be useful for differentiating PCa from CP. p53 Mutations are found in 4%-50% in PJ from patients with PCa but are not detectable in PJ from CP, suggesting that the specificity of p53 mutations is very high for PCa. Furthermore, p53 mutations were detected in 7 of 15 (47%) patients with PCa in which the PJ cytologic diagnosis was negative. Telomerase (TE) activity or its catalytic subunit, h-TERT, was reportedly positive >80% in PJ from PCa but was detected in <20% of PJ from CP. TE activity in PJ from CP originates from lymphocytes. The development and application of these new genetic and epigenetic markers with high specificity and sensitivity for PCa in serum and PJ will significantly improve our diagnostic accuracy.