title: Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors.
abstract: Well-differentiated neuroendocrine tumors (WDNET) of the gastrointestinal tract, pancreas, and lung are histologically similar. Thus, predicting the site of origin of a metastasis is not possible on morphologic grounds. Prior immunohistochemical studies of WDNET have yielded conflicting results, and pancreatic and duodenal homeobox factor-1 (PDX-1) has not previously been evaluated in this context. We therefore analyzed the expression of CDX-2, PDX-1, TTF-1, and neuroendocrine secretory protein-55 (NESP-55), a recently described member of the chromogranin family, in primary and metastatic WDNET. In total, 64 gastrointestinal carcinoids (5 stomach; 5 duodenum; 31 ileum; 11 appendix; and 12 rectum); 39 pancreatic endocrine tumors (PET); and 20 pulmonary carcinoid tumors were studied. PET were positive for NESP-55 (16/39) and PDX-1 (11/39); 3/31 also showed heterogeneous positivity for CDX-2. Ileal carcinoids were exclusively positive for CDX-2 (30/31) and negative for all other markers. Appendiceal carcinoids were uniformly positive for CDX-2 (11/11). All rectal carcinoids were negative for CDX-2 and TTF-1; 2/12 were positive for PDX-1, and 1/12 for NESP-55. The gastric and duodenal carcinoids were only positive for PDX-1 (7/10). TTF-1 positivity was confined to pulmonary carcinoids (7/20); 1/20 was positive for NESP-55; and all were negative for CDX-2 and PDX-1. NESP-55 and PDX-1 positivity, in the presence of negative CDX-2 and TTF-1, was 97% specific for PET. The sensitivity and specificity of CDX-2 positivity for predicting an ileal primary, when PDX-1, NESP-55, and TTF-1 were negative, was 97% and 91%, respectively. TTF-1 positivity was confined to pulmonary carcinoids in our study but was present in only about a third of cases. A panel of these 4 markers may be useful in predicting the primary site of metastatic WDNET.
authors.affiliation: Dartmouth Medical School, Dartmouth-Hitchcock Medical Center Lebanon, NH, USA.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D002864:Chromogranins; D004268:DNA-Binding Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D019084:Fluorescent Antibody Technique, Indirect; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; D002864:Chromogranins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; C504003:TTF1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs