Molecular testing in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with high mortality. Patients with a disease limited to the pancreas have a chance for a cure, but the likelihood of remission decreases if the cancer involves adjacent vessels or lymph nodes. Eventually the disease progresses to a terminal stage when the cancer is locally advanced and unresectable or when there are distant metastases. To prevent progression, the current goal is to detect PDAC in its earliest stages. Diagnostic biomarkers for pancreatic cancer must fulfill this criterion with a high sensitivity, specificity, and accuracy, but also be able to distinguish PDAC from other pancreatic conditions. Some of these conditions are associated with an increased risk of PDAC, but do not have the invasive disease at the time of identification. Although genetic alterations are well described in chronic pancreatitis, mucinous cystic neoplasms, and intraductal papillary mucinous neoplasms, the natural progression of these lesions to PDAC is not well understood. Over the last three decades the search for adequate diagnostic biomarkers for PDAC has closely followed the establishment of new biotechnological methods. Early methods detected protein biomarkers using enzyme-linked immunosorbent assay and Western blots. Subsequently the PCR was developed and found to have utility for the detection of genetic alterations. The latest chromatographic methods, gene-chips, and protein-chips enable a very broad search for diagnostic biomarkers including genome-wide screening. Most recently, epigenetic changes were found to be significantly altered in PDAC. Several studies have shown that panels of biomarkers increase sensitivity, specificity, and diagnostic accuracy in the diagnosis of PDAC, reflecting the fact that PDAC exhibits significant heterogeneity. Despite similar anatomic location cancers can have different biological backgrounds reflecting distinct molecular pathways to tumorigenesis, and therefore require different diagnostic biomarkers.