title: PDX-1, CDX-2, TTF-1, and CK7: a reliable immunohistochemical panel for pancreatic neuroendocrine neoplasms.
abstract: Neuroendocrine tumors (NETs) occur in virtually all sites of the body. As NETs arising in different organs share similar morphologic features, distinguishing metastatic from primary NETs on the basis of morphologic grounds alone is difficult. Pancreatic duodenal homeobox 1 (PDX-1) is a Hox-type transcription factor that is essential for both exocrine and endocrine pancreatic differentiation and maintenance of β-cell function. We investigated PDX-1 as an immunohistochemical (IHC) marker in primary pancreatic NETs. Eighty primary NETs [25 pancreatic, 29 bronchopulmonary, and 26 in the gastrointestinal (GI) tract] and 13 metastatic NETs in the liver were studied. Clinical and radiologic data were reviewed to confirm the stated primary sites. IHC analysis for PDX-1, CDX-2, thyroid transcription factor-1 (TTF-1), keratin 7 (CK7), and keratin 20 (CK20) was performed, and the results were based on review blinded to the primary sites. PDX-1 was seen in 18 of 25 (72%) pancreatic NETs; in contrast, only 3 of 29 (10%) bronchopulmonary NETs and 1 of 26 (4%) GI NETs were positive. PDX-1 was therefore 93% specific and 72% sensitive for pancreatic NETs. TTF-1 was expressed only in bronchopulmonary NETs; all other NETs were negative for TTF-1. CK7 was also very specific (92%) and moderately sensitive (66%) for bronchopulmonary NETs. CDX-2 was seen in 22 of 26 (85%) cases of GI NETs and in only 1 of 51 (2%) cases of extra-GI NETs. Thus, CDX-2 was 98% specific and 85% sensitive for GI NETs. In terms of metastatic NETs found in the liver, PDX-1 was positive in 5 of 5 cases of metastatic pancreatic NETs and 2 of 2 cases of metastatic duodenal NETs. PDX-1 is highly specific, with very good overall diagnostic accuracy for pancreatic NETs. An IHC panel including PDX-1, CDX-2, TTF-1, CK7, and CK20 may be useful in distinguishing NETs of pancreatic origin from other primaries.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, 98195-6100, USA.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Chan
authors.forename: Jacob
authors.initials: J
authors.lastname: Alexander
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Jain
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000378:metabolism; D053554:Keratin-20 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; C504003:TTF1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein