Molecular versus Conventional Markers in Pancreatic Cancer

Abstract

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.

Pancreatic cancer cell-derived vascular endothelial growth factor is biologically activein vitro and enhances tumorigenicityin vivo

“…30 As a result, the median survival time for these patients is 4 to 6 months after diagnosis. 31 VEGF may have a role in PDAC since its presence in the pancreatic cancer cells is associated with increased blood vessel number, larger tumor size, enhanced local tumor spread, 28 increased incidence of liver metastasis and decreased patient survival. 32,33 However, PDAC are usually not highly vascular tumors, and it has not been firmly established whether VEGF enhances pancreatic tumor growth in vivo.…”

Orthotopic Model of Human Pancreatic Ductal Adenocarcinoma and Cancer Cachexia in Nude Mice

“…Record weights of the primary tumor with attached spleen, liver, and other involved organs for each mouse. Immunostaining for the pancreas-selective antigen CA19-9 may be performed (Friess et al, 1997) to confirm the pancreatic origin of metastatic lesions. For the color version of this figure go to http://www.currentprotocols.com.…”

“…Figure 14.3.2 Hemotoxylin and eosin histological sections of a liver metastasis revealing (A)very little normal liver present in this section, as the pancreatic metastatic tissue has displaced the normal liver tissue; (B) primary pancreatic ductal carcinoma (arrows mark islands of tumor cells among normal glandular tissue); (C) peripancreatic (invasive) metastasis (arrows mark islands of tumor cells); and (D) mesenteric lymph node metastasis (arrows mark islands of tumor cells) from orthotopically-grafted COLO-357 human pancreatic carcinoma tissue. Immunostaining for the pancreas-selective antigen CA19-9 may be performed(Friess et al, 1997) to confirm the pancreatic origin of metastatic lesions. For the color version of this figure go to http://www.currentprotocols.com.…”

Growth factors and their receptors in pancreatic cancer

“…Acidic FGF (FGF 1 or aFGF) and basic FGF (FGF 2 or bFGF) are the prototypes of this growth factor family. This family also includes int-2 (FGF 3), hst (FGF 4 or Kaposi FGF), FGF 5, FGF 6, keratinocyte growth factor (FGF 7 or KGF), androgen-induced growth factor (FGF 8), glia-activating factor (FGF 9), and FGF 10 [105]. Signaling by the FGFs is mediated by a dual-receptor system that consists of four high-affinity transmembrane tyrosine-kinase FGF receptors (FGFRs) that function as signaling molecules to transmit the effects of FGFs, as well as by low-affinity heparansulfate-proteoglycans (HSPGs) that are devoid of signaling capabilities but enhance ligand presentation to FGFRs [99][100][101][102][103][104].…”