Korean J Hepatobiliary Pancreat Surg.
2004 Jun;8(2):69-75.
Molecular Diagnosis and Tumor Markers in Pancreatic Cancer
- Affiliations
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- 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. jkryu@snu.ac.kr
Abstract
- Pancreatic cancer is a devastating disease with a fatal prognosis due to late diagnosis. Current imaging studies are inadequate for early detection and CA 19-9, the best tumor marker thus far, has low sensitivity in small pancreatic cancer, so the use of new markers is our most promising approach. Activation of the proto-oncogene K-ras and inactivation of the tumor suppressor genes p53, p16 and SMAD4 are characteristics for pancreatic cancer. K-ras mutation can be detected from pancreatic juice in 55~79% of patients with pancreatic cancer but can occur in the setting of chronic pancreatitis up to 32%. Telomerase activity in pancreatic juice can be used to distinguish between cancer and pancreatitis. The progression model of pancreatic cancer proposes that pancreatic intraepithelial neoplasia is the pre-cancerous lesion and this model is important for developing screening tools to detect early curable cancer. Pancreatic cancer harbors aberrant methylation of many cancer-related genes and detection of DNA hypermethylation by methylation specific PCR is attractive new candidate suitable for early detection. Recent large- scale gene expression studies can be done using cDNA and oligonucleotide microarrays and serial analysis of gene expression. Hundreds of overexpressed genes were already identified in pancreatic cancer. Large-scale analysis of proteins in biologic samples is possible by proteomics which has been applied to discovery proteins that could be used as potential markers. It is hoped that the understanding of genetic alterations and development of high throughput technologies will lead to the rapid discovery of biomarkers that will save lives by enabling aggressive therapy at the early stage.