Serum Tumor Markers and Molecular Biological Diagnosis in Pancreatic Cancer

Abstract

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.

TPS, CA 19-9, VEGF-A, and CEA as Diagnostic and Prognostic Factors in Patients with Mass Lesions in the Pancreatic Head

“…The tumour markers are rather crude measures of resectability and prognosis in patients with pancreatic cancer. Despite the fact the marker levels in our study were overall slightly lower than in previous studies of the same markers applied as diagnostic (17,19,21,22) and prognostic markers (4,10,14,23), none of the included patients were found to fit for pancreatic resection.…”

Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of pancreatic carcinoma patients

“…Up to now, several markers such as K-ras, p53 and CEA failed as serum marker for a differential diagnosis [17,42] . CK 19-9 is the best characterized serum marker but has no absolute specificity.…”

“…However, expressions of these antigens have also been reported in cholangitis, chronic pancreatitis and various g astrointestinal tumors [17] . Various studies used cytokeratin-19 (CK-19) for pancreatic cell detection.…”

Prognostic and Therapeutic Significance of Carbohydrate Antigen 19-9 as Tumor Marker in Patients with Pancreatic Cancer

“…In PC, new markers like genetic alterations and also other serum tumor antigens (e.g. CA 72-4 or CA 242) must be further investigated and both their diagnostic and prognostic role must be defined by comparative studies with CA 19-9 [57, 58]. Pretreatment alterations (like S100A6 [59]) as well as kinetics of novel apoptotic markers like nucleosomes [60] during therapy may have prognostic significance, and thus may serve as helpful tools in therapeutic decisions in this harmful disease.…”