Abstract
Pancreatic cancer is a uniquely challenging cancer. First, it is a deadly cancer. Pancreatic cancer is the fourth leading cause of cancer death in men and in women, and, despite advances in the treatment of other types of cancer, pancreatic cancer continues to have one of the highest mortality rates of any malignancy. Each year in the U.S. approx 29,000 patients are diagnosed with pancreatic cancer, and approx 29,000 will die of their disease (1). The poor prognosis for patients with pancreatic cancer is, in large part, due to the fact that almost all patients are diagnosed at an advanced stage of disease, as no known tumor markers exist that could be used to screen for pancreatic cancer at an earlier, potentially curative stage. This is a particular problem for those patients with a strong familial history of pancreatic cancer, who may have up to a 57-fold greater risk of developing pancreatic cancer in their lifetime (2,3). Second, even when a mass caused by a pancreatic cancer is identified, it can be very difficult to establish a definitive diagnosis. Deadly infiltrating adenocarcinomas of the pancreas can be so well differentiated that it can be difficult, and even at times impossible, to distinguish cancer from reactive changes histologically. Third, even when the diagnosis can be firmly established, pancreatic cancer simply does not respond to current chemotherapeutic or radiation therapies. Perhaps more than any other tumor type, a better understanding of the gene expression of pancreatic cancer is urgently needed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Greenlee, R. T., Hill-Harmon, M. B., Murray, T., and Thun, M. (2001) Cancer Statistics, 2001. CA Cancer J. Clin. 51, 16–36.
Tersmette, A. C., Petersen, G. M., Offerhaus, G. J. A., et al. (2001) Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin. Cancer Res. 7, 738–744.
Giardiello, F. M., Welsh, S. B., Hamilton, S. R., et al. (1987) Increased risk of cancer in the Peutz-Jeghers syndrome. N. Engl. J. Med. 316, 1511–1514.
Wilentz, R. E., Geradts, J., Maynard, R., et al. (1998) Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: Loss of intranuclear expression. Cancer Res. 58, 4740–4744.
Wilentz, R. E., Iacobuzio-Donahue, C. A., Argani, P., et al. (2000) Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 60, 2002–2006.
Hruban, R. H., Adsay, N. V., Albores-Saavedra, J., et al. (2001) Pancreatic intraepithelial neoplasia (Panin): a new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 25, 579–586.
Hruban, R. H., Wilentz, R. E., and Kern, S. E. (2000) Genetic progression in the pancreatic ducts. Am. J. Pathol. 156, 1821–1825.
Redston, M. S., Caldas, C., Seymour, A. B., et al. (1994) p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res. 54, 3025–3033.
Schutte, M., Hruban, R. H., Geradts, J., et al. (1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 57, 31263130.
Hruban, R. H., van Mansfeld, A. D. M., Offerhaus, G. J. A., et al. (1993) K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am..1. Pathol. 143, 545–554.
Wilentz, R. E., Su, G. H., Dai, J. L., et al. (2000) Immunohistochemical labeling for Dpc4 mirrors genetic status in pancreatic: a new marker of DPC4 inactivation. Am. J. Pathol. 156, 37–43.
Ellenrieder, V., Hendler, S. F., Ruhland, C., Boeck, W., Adler, G., and Gress, T. M. (2001) TGF-beta-induced invasiveness of pancreatic cancer cells is mediated by matrix metalloproteinase-2 and the urokinase plasminogen activator system. Int. J. Cancer 93, 204–211.
Ebert, M., Yokoyama, M., Friess, H., Kobrin, M. S., Buehler, M. W., and Korc, M. (1995) Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int. J. Cancer 62, 529–535.
Friess, H., Yamanaka, Y., Buehler, M., et al. (1993) Enhanced expression of the type II transforming growth factor beta receptor in human pancreatic cancer cells without alteration of type III receptor expression. Cancer Res. 53, 2704–2707.
Goggins, M., Schutte, M., Lu, J., et al. (1996) Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 56, 5360–5364.
Pour, P. M. and Schmied, B. (1999) The link between exocrine pancreatic cancer and the endocrine pancreas. Int. J. Pancreatol. 25, 77–87.
Rao, M. S., Yeldandi, A. V., and Reddy, J. K. (1990) Stem cell potential of ductular and periductular cells in the adult rat pancreas. Cell Differ. Dey. 29, 155–163.
Solcia, E., Capella, C., and Klöppel, G. (1997) Atlas of Tumor Pathology: Tumors of the Pancreas. 3rd ed. Armed Forces Institute of Pathology, Washington, D.C.
Balague, C., Audie, J. P., Porchet, N., and Real, F. X. (1995) In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Gastroenterology 109, 953–964.
Shimizu, M., Saitoh, Y., Ohyanagi, H., and Itoh, H. (1990) Immunohistochemical staining of pancreatic cancer with CA19–9, KM01, unabsorbed CEA, and absorbed CEA. Arch. Pathol. Lab. Med. 114, 195–200.
Terada, T., Ohta, T., Sasaki, M., Nakanuma, Y., and Kim, Y. S. (1996) Expression of MUC apomucins in normal pancreas and pancreatic tumours. J. Pathol. 180, 160–165.
Ritts, R. E. and Pitt, H. A. (1998) CA19–9 in pancreatic cancer. Surg. Clin. N. Am. 7, 93–101.
Ross, D. T., Scherf, U., Eisen, M. B., et al. (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 24, 227–235.
Iacobuzio-Donahue, C. A., Ryu, B., Hruban, R. H., and Kern, S. E. (2002) Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neo-plastic cells at the site of primary invasion. Am. J. Pathol. 160, 91–99.
Ryu, B., Jones, J., Hollingsworth, M. A., Hruban, R. H., and Kern, S. E. (2001) Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 61, 1833–1838.
Hahn, S. A., Seymour, A. B., Hogue, A. T. M. S., et al. (1995) Allelotype of pancreatic adenocarcinoma using xenograft enrichment. Cancer Res. 55, 4670–4675.
Ryu, B., Jones, J., Hollingsworth, M. A., Hruban, R. H., and Kern, S. E. (2002) Relationships and identification of differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. Cancer Res. 62, 5351–5357.
Velculescu, V. E., Zhang, L., Vogelstein, B., and Kinzler, K. W. (1995) Serial analysis of gene expression. Science 270, 484–487.
Zhou, W., Sokoll, L. J., Bruzek, D. J., et al. (1998) Identifying markers for pancreatic cancer by gene expression analysis. Cancer Epidemiol. Biomarkers Prey. 7, 109–112.
Rosty, C., Ueki, T., Argani, P., et al. (2002) Overexpression of S l 00A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am. J. Pathol. 160, 45–50.
Iacobuzio-Donahue, C. A., Maitra, A., Olsen, M., et al. (2003) Exploration of global gene expression of pancreatic adenocarcinoma by cDNA microarray analysis. Am. J. Pathol.,in press.
Heiskala, M., Peterson, P. A., and Yang, Y. (2001) The roles of claudin superfamily proteins in paracellular transport. Traffic 2, 93–98.
Kikkawa, Y., Sanzen, N., Fujiwara, H., Sonnenberg, A., and Sekiguchi, K. (2000) Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. J. Cell Sci. 113, 869–876.
Schussler, M. H., Skoudy, A., Ramaekers, F., and Real, F. X. (1992) Intermediate filaments as differentiation markers of normal pancreas and pancreas cancer. Am. J. Surg. Pathol. 140, 559–568.
DiGiuseppe, J. A., Redston, M. S., Yeo, C. J., Kern, S. E., and Hruban, R. H. (1995) p53-independent expression of the cyclin-dependent kinase inhibitor p21 in pancreatic carcinoma. Am. J. Pathol. 147, 884–888.
Sparks, A. B., Morin, P. J., Vogelstein, B., and Kinzler, K. W. (1998) Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 58, 1130–1134.
Ruse, M., Lambert, A., Robinson, N., Ryan, D., Shon, K. J., and Eckert, R. L. (2001) S l 00A7, S100A10, and S100A11 are transglutaminase substrates. Biochemistry 40, 3167–3173.
Ellenrieder, V., Alber, B., Lacher, U., et al. (2000) Role of MT-MMPs and MMP-2 in pancreatic cancer progression. Int. J. Cancer 85, 14–20.
Iacobuzio-Donahue, C. A., Maitra, A., Shen-Ong, G. L., et al. (2002) Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am. J. Pathol. 160, 1239–1249.
Morita, K., Furuse, M., Fujimoto, K., and Tsukita, S. (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc. Natl. Acad. Sci. USA 96, 511–516.
Carrio, M., Romagosa, A., Mercade, E., et al. (1999) Enhanced pancreatic tumor regression by a combination of adenovirus and retrovirus-mediated delivery of the herpes simplex virus thymidine kinase gene. Gene Ther. 6, 547–553.
Ripani, E., Sacchetti, A., Corda, D., and Alberti, S. (1998) Human Trop-2 is a tumor-associated calcium signal transducer. Int. J. Cancer 76, 671–676.
Namima, M., Takeuchi, K., Watanabe, Y., et al. (1998) Localization of GTPase-activating protein-(GAP) like immunoreactivity in mouse cerebral regions. Mol. Chem. Neuropathol. 35, 157–172.
Donato, R. (2001) 5100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int. J. Biochem. Cell Biol. 33, 637–668.
Tseng, Y., Fedorov, E., McCaffery, J. M., Almo, S. C., and Wirtz, D. (2001) Micro-mechanics and ultrastructure of actin filament networks crosslinked by human fascin: a comparison with alpha-actinin. J. Mol. Biol. 310, 351–366.
Goldstein, N. S. and Bassi, D. (2001) Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am. J. Clin. Pathol. 115, 695–702.
Lai, F., Fernald, A. A., Zhao, N., and Le Beau, M. M. (2000) cDNA cloning, expression pattern, genomic structure and chromosomal location of RAB6KIFL, a human kinesin-like gene. Gene 248, 117–125.
Sato, T. K., Overduin, M., and Emr, S. D. (2001) Location, location, location: membrane targeting directed by PX domains. Science 294, 1881–1885.
Schwartz, M. A. (2001) Integrin signaling revisited. Trends Cell Biol. 11, 466–470.
Tanner, M., Jarvinen, P., and Isola, J. (2001) Amplification of HER-2/neu and topoisomerase Ilalpha in primary and metastatic breast cancer. Cancer Res. 61, 5345–5348.
Ikeda, M., Yu, W., Hirai, M., et al. (2000) cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2: its mRNA expression, subcellular distribution, and chromosomal localization. Biochem. Biophys. Res. Commun. 275, 493–502.
Downing, J. R. (2001) AML1/CBFbeta transcription complex: its role in normal hematopoiesis and leukemia. Leukemia 15, 664–665.
Hosoi, Y. and Kapp, L. N. (1994) Expression of a candidate ataxia-telangiectasia group D gene in cultured fibroblast cell lines and human tissues. Int. J. Radiat. Biol. 66 (6 Suppl), S71 – S76.
Gress, T. M., Muller-Pillasch, F., Lerch, M. M., et al. (1994) Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis. Z. Gastroenterol. 32, 221–225.
Dafforn, T. R., Della, M., and Miller, A. D. (2001) The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis. J. Biol. Chem. 276, 49,310–49, 319.
Rosty, C., Christa, L., Kuzdzal, S., et al. (2002) Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated-protein I (HIP/PAP-1) as a biomarker for pancreatic adenocarcinoma by protein biochip technology. Cancer Res. 62, 1868–1875.
Tascilar, M., Offerhaus, G. J., Altink, R., et al. (2001) Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct. Am. J. Clin. Pathol. 116, 831–837.
Jaffee, E. M., Hruban, R. H., Biedrzycki, B., et al. (2001) Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J. Clin. Oncol. 19, 145–156.
Jaffee, E. M., Schutte, M., Gossett, J., et al. (1998) Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials. Cancer J. Sci. Am. 4, 194–203.
McDevitt, M. R., Ma, D., Lai, L. T., et al. (2001) Tumor therapy with targeted atomic nanogenerators. Science 294, 1537–1540.
Argani, P., Rosty, C., Reiter, R. E., et al. (2001) Discovery of new markers of cancer through serial analysis of gene expression (SAGE): prostate stem cell antigen (PSCA) is overexpressed in pancreatic adenocarcinoma. Cancer Res. 61, 4320–4324.
Argani, P., Iacobuzio-Donahue, C., Ryu, B., et al. (2001) Mesothelin is expressed in the vast majority of adenocarcinomas of the pancreas: identification of a new cancer marker by serial analysis of gene expression (SAGE). Clin. Cancer Res. 7, 3862–3868.
Carrio, M., Mazo, A., Lopez-Iglesias, C., Estivill, X., and Fillat, C. (2001) Retrovirusmediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: implications for gene therapy. Int. J. Cancer 94, 81–88.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Iacobuzio-Donahue, C.A., Hruban, R.H. (2003). Expression Profiling of Pancreatic Ductal Adenocarcinoma. In: Ladanyi, M., Gerald, W.L. (eds) Expression Profiling of Human Tumors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-386-6_14
Download citation
DOI: https://doi.org/10.1007/978-1-59259-386-6_14
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-375-6
Online ISBN: 978-1-59259-386-6
eBook Packages: Springer Book Archive