title: Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin.
abstract: Neuroendocrine tumors can present as liver metastases before discovery of the primary tumor. Islet 1 and PAX8 have recently been proposed as markers for neuroendocrine tumors of pancreatic origin. In this study, we compared the utility of Islet 1 and PAX8 in distinguishing pancreatic neuroendocrine tumors from neuroendocrine tumors of other sites and determined the usefulness of an immunohistochemical panel, including TTF1, CDX2, Islet 1 and/or PAX8, in identifying metastatic pancreatic neuroendocrine tumors. A total of 110 primary neuroendocrine tumors (33 pancreatic, 31 pulmonary, 23 ileal, 14 rectal, and 9 gastric) and 73 metastatic neuroendocrine tumors (28 pancreatic, 5 pulmonary, 37 ileal, 1 rectal, 1 colonic, and 1 duodenal) were studied. Islet 1 and PAX8 were positive in 27/33 (82%) and 29/33 (88%), respectively, of primary pancreatic neuroendocrine tumors, and in 19/28 (68%) and 15/28 (54%), respectively, of metastatic pancreatic neuroendocrine tumors. No cases of primary (0/23) or metastatic (0/37) ileal neuroendocrine tumors were positive with either Islet 1 or PAX8. There was Islet 1 positivity in 2/31 (6%) primary pulmonary, 12/14 (86%) primary rectal, and 1/1 metastatic rectal neuroendocrine tumors, and PAX8 positivity in 7/31 (23%) primary pulmonary, 11/14 (79%) primary rectal, and 2/9 (22%) primary gastric neuroendocrine tumors. ROC curve analysis incorporating sensitivity and specificity data of immunohistochemical panels for metastatic pancreatic neuroendocrine tumors showed that a four-stain panel, including Islet 1, PAX8, TTF1, and CDX2 significantly outperformed a three-stain panel composed of PAX8, TTF1, and CDX2 (P=0.019), and also showed a trend for better performance compared with a three-stain panel composed of Islet 1, TTF1, and CDX2 (P=0.072). Both Islet 1 and PAX8 are reliable immunohistochemical markers for pancreatic neuroendocrine tumors and would be useful adjuncts to other markers (TTF1, CDX2) currently used to work up a metastatic neuroendocrine tumor of unknown primary.
authors.affiliation: Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. jamie.koo@cshs.org
authors.forename: Jamie
authors.initials: J
authors.lastname: Koo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Mertens
authors.forename: James M
authors.initials: JM
authors.lastname: Mirocha
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
authors.forename: Deepti
authors.initials: D
authors.lastname: Dhall
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D000071616:CDX2 Transcription Factor; D004268:DNA-Binding Proteins / Q000032:analysis; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000032:analysis*; D015141:Los Angeles; D009382:Neoplasms, Unknown Primary / Q000737:chemistry* / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000737:chemistry* / Q000556:secondary; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C504003:TTF1 protein, human; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1