title: Comparison of PAX6 and PAX8 as immunohistochemical markers for pancreatic neuroendocrine tumors.
abstract: To compare the utility of PAX6 and PAX8 as immunohistochemical markers for neuroendocrine tumors (NETs) of pancreatic origin, we performed PAX6 and PAX8 immunostains on 178 NETs, including 110 primary NETs (26 pancreatic, 10 gastric, 12 duodenal, 22 jejuno-ileal, 10 rectal, 30 pulmonary) and 68 NETs metastatic to the liver (24 pancreatic, 1 duodenal, 37 jejuno-ileal, 1 rectal, 5 pulmonary). Among primary NETs, PAX6 and PAX8 were positive in 65 % (17/26) and 73 % (19/26) of pancreatic, 0 % (0/10) and 10 % (1/10) of gastric, 92 % (11/12) and 92 % (11/12) of duodenal, 0 % (0/22) and 0 % (0/22) of jejuno-ileal, 90 % (9/10) and 80 % (8/10) of rectal, and 0 % (0/30) and 23 % (7/30) of pulmonary NETs, respectively. PAX6 and PAX8 positivity was seen in 46 % (11/24) and 50 % (12/24) of metastatic pancreatic NETs to the liver, respectively. None of the nonpancreatic NETs metastatic to the liver were immunoreactive for either PAX6 or PAX8. PAX6 showed a slightly but statistically significant higher specificity for pancreatic NETs than did PAX8 (P = 0.039), while the sensitivities were similar (P = 0.51). PAX6 had the additional advantages over PAX8 of not exhibiting nonspecific cytoplasmic staining of tumor cells and only infrequently staining background lymphocytes. Since rectal NETs rarely present with metastatic disease, positive staining of a metastatic NET of unknown primary origin for PAX6 and/or PAX8 favors a pancreatic or duodenal origin. This information may be helpful in directing further diagnostic studies to identify the primary site of the metastatic tumor.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA, jinpinglai@slu.edu.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Lai
authors.forename: Richard B
authors.initials: RB
authors.lastname: Mertens
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.forename: Jamie
authors.initials: J
authors.lastname: Koo
authors.forename: Mariza
authors.initials: M
authors.lastname: Venturina
authors.forename: Fai
authors.initials: F
authors.lastname: Chung
authors.forename: Allen B
authors.initials: AB
authors.lastname: Mendez
authors.forename: Melissa
authors.initials: M
authors.lastname: Kahn
authors.forename: Deepti
authors.initials: D
authors.lastname: Dhall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005136:Eye Proteins / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary; D000071841:PAX6 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis* / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary; D012097:Repressor Proteins / Q000032:analysis* / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins