This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bloomston, M. Articles by Zervos, E. E. Search for Related Content PubMed PubMed Citation Articles by Bloomston, M. Articles by Zervos, E. E.

Identification of Molecular Markers Specific for Pancreatic Neuroendocrine Tumors by Genetic Profiling of Core Biopsies

From the Department of Surgery (MB, AD, ASR, TJY, EEZ) and Department of Pathology (MR), University of South Florida College of Medicine, and the Department of Interdisciplinary Oncology (SE, TJY), H. Lee Moffitt Cancer Center, Tampa, Florida; and The Institute for Genomic Research (IY), Rockville, Maryland.

Correspondence: Address correspondence and reprint requests to: Emmanuel E. Zervos, MD, Assistant Professor of Surgery, Moffitt Cancer Center, 12902 Magnolia Drive, MRC-30037, Tampa, Florida 33612; e-mail: ezervos{at}hsc.usf.edu

Background: There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies.

Methods: Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers.

Results: Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis.

Conclusion: We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.

Key Words: Genetics • Microarray • Neuroendocrine • Pancreas

This article has been cited by other articles:

				T. R Halfdanarson, J. Rubin, M. B Farnell, C. S Grant, and G. M Petersen Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors Endocr. Relat. Cancer, June 1, 2008; 15(2): 409 - 427. [Abstract] [Full Text] [PDF]

				E.-M. Duerr, Y. Mizukami, A. Ng, R. J Xavier, H. Kikuchi, V. Deshpande, A. L Warshaw, J. Glickman, M. H Kulke, and D. C Chung Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis Endocr. Relat. Cancer, March 1, 2008; 15(1): 243 - 256. [Abstract] [Full Text] [PDF]

				M. Kidd, B. Nadler, S. Mane, G. Eick, M. Malfertheiner, M. Champaneria, R. Pfragner, and I. Modlin GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR Physiol Genomics, August 20, 2007; 30(3): 363 - 370. [Abstract] [Full Text] [PDF]

				M. Bloomston, W. L. Frankel, F. Petrocca, S. Volinia, H. Alder, J. P. Hagan, C.-G. Liu, D. Bhatt, C. Taccioli, and C. M. Croce MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis JAMA, May 2, 2007; 297(17): 1901 - 1908. [Abstract] [Full Text] [PDF]

				G Capurso, S Lattimore, T Crnogorac-Jurcevic, F Panzuto, M Milione, V Bhakta, N Campanini, S M Swift, C Bordi, G D. Fave, et al. Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets. Endocr. Relat. Cancer, June 1, 2006; 13(2): 541 - 558. [Abstract] [Full Text] [PDF]

				A. Horvath, L. Mathyakina, Q. Vong, V. Baxendale, A. L. Y. Pang, W.-Y. Chan, and C. A. Stratakis Serial Analysis of Gene Expression in Adrenocortical Hyperplasia Caused by a Germline PRKAR1A Mutation J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 584 - 596. [Abstract] [Full Text] [PDF]