Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays

Journal Article

Purpose: Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. Experimental Design: RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90% purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP ( for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Results: Sixty-six transcripts were overexpressed ≥3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed ≤3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down-regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93%) versus primary PEN lesions (60%), P = 0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55%) compared with primary PEN lesions (24%; P = 0.14). Conclusions: Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms.

Duke Authors

Cited Authors

  • Maitra, A; Hansel, DE; Argani, P; Ashfaq, R; Rahman, A; Naji, A; Deng, S; Geradts, J; Hawthorne, LA; House, MG; Yeo, CJ

Published Date

  • December 1, 2003

Published In

Volume / Issue

  • 9 / 16 I

Start / End Page

  • 5988 - 5995

International Standard Serial Number (ISSN)

  • 1078-0432

Citation Source

  • Scopus