title: Gene expression profiling identifies markers of ampullary adenocarcinoma.
abstract: Ampullary adenocarcinoma is an aggressive cancer with a poor prognosis. Without surgical resection, ampullary adenocarcinomas can be difficult to distinguish from ampullary adenomas. The aim of this study was to identify differentially expressed genes in ampullary adenocarcinoma in order to identify candidate markers of the disease. The Affymetrix Human Genome U133 GeneChip set (HG-U133A and HG-U133B) was used to obtain gene expression profiles of 5 ampullary adenocarcinomas and 10 normal duodenal samples. Using fold change analysis we identified 235 fragments expressed at least fivefold higher in ampullary cancers than in normal duodenum. The expression profiles of eight candidate overexpressed genes (osteopontin, mesothelin, tissue inhibitor of metalloproteinases 1, mucin-1, mucin-5, fascin, heat shock protein 47, fibronectin 1) were confirmed by immunohistochemistry or in situ hybridization on tissue microarrays (TMA) containing 54 ampullary adenocarcinomas. One of these genes, osteopontin, was expressed 27-fold higher levels in ampullary adenocarcinomas compared to normal duodenum by genechip analysis. We therefore determined serum osteopontin levels in patients with ampullary neoplasms, patients with other periampullary diseases and in normal controls. Mean preoperative serum osteopontin levels as measured by competitive ELISA were 906 +/- 268 ng/ml in patients with ampullary cancer, 867 +/- 160 ng/ml in patients with an ampullary adenoma, 327.1 +/- 195.6 ng/ml in patients with nonmalignant periampullary diseases and 204 +/- 65 ng/ml in age-matched healthy controls (p < 0.001). Measurement of markers of ampullary cancer such as osteopontin may aid in the early detection and differential diagnosis of patients with periampullary lesions.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA.
authors.forename: N Tjarda
authors.initials: NT
authors.lastname: Van Heek
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Jens
authors.initials: J
authors.lastname: Koopmann
authors.forename: Neil
authors.initials: N
authors.lastname: Fedarko
authors.forename: Alka
authors.initials: A
authors.lastname: Jain
authors.forename: Ayman
authors.initials: A
authors.lastname: Rahman
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Johan A
authors.initials: JA
authors.lastname: Offerhaus
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Karin D
authors.initials: KD
authors.lastname: Berg
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014670:Ampulla of Vater / Q000601:surgery*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003138:Common Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016577:Pancreaticoduodenectomy; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin