title: Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2.
abstract: We recently identified the transcription factor (TF) islet 1 gene product (ISL1) as a marker for well-differentiated pancreatic neuroendocrine tumors (P-NETs). In order to better understand the expression of the four TFs, ISL1, pancreatico-duodenal homeobox 1 gene product (PDX1), neurogenin 3 gene product (NGN3), and CDX-2 homeobox gene product (CDX2), that mainly govern the development and differentiation of the pancreas and duodenum, we studied their expression in hormonally defined P-NETs and duodenal (D-) NETs. Thirty-six P-NETs and 14 D-NETs were immunostained with antibodies against the four pancreatic hormones, gastrin, serotonin, calcitonin, ISL1, PDX1, NGN3, and CDX2. The TF expression pattern of each case was correlated with the tumor's hormonal profile. Insulin-positive NETs expressed only ISL1 (10/10) and PDX1 (9/10). Glucagon-positive tumors expressed ISL1 (7/7) and were almost negative for the other TFs. Gastrin-positive NETs, whether of duodenal or pancreatic origin, frequently expressed PDX1 (17/18), ISL1 (14/18), and NGN3 (14/18). CDX2 was mainly found in the gastrin-positive P-NETs (5/8) and rarely in the D-NETs (1/10). Somatostatin-positive NETs, whether duodenal or pancreatic in origin, expressed ISL1 (9/9), PDX1 (3/9), and NGN3 (3/9). The remaining tumors showed labeling for ISL1 in addition to NGN3. There was no association between a particular TF pattern and NET features such as grade, size, location, presence of metastases, and functional activity. We conclude from our data that there is a correlation between TF expression patterns and certain hormonally defined P-NET and D-NET types, suggesting that most of the tumor types originate from embryologically determined precursor cells. The observed TF signatures do not allow us to distinguish P-NETs from D-NETs.
authors: Department of Pathology, Assaf Harofeh Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Gratiana
authors: G
authors: Hermann
authors: Björn
authors: B
authors: Konukiewitz
authors: Anja
authors: A
authors: Schmitt
authors: Aurel
authors: A
authors: Perren
authors: Günter
authors: G
authors: Klöppel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071616:CDX2 Transcription Factor; D002116:Calcitonin / Q000096:biosynthesis; D004379:Duodenal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005755:Gastrins / Q000096:biosynthesis; D005934:Glucagon / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000096:biosynthesis; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010191:Pancreatic Polypeptide / Q000096:biosynthesis; D013004:Somatostatin / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; D002116:Calcitonin; D005755:Gastrins; D005934:Glucagon; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010191:Pancreatic Polypeptide; D013004:Somatostatin; D015534:Trans-Activators; D014157:Transcription Factors; C491270:CDX2 protein, human; C498695:NEUROG3 protein, human; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein