title: Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors.
abstract: Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcription factor that is expressed in the developing thyroid, respiratory epithelium, and diencephalon. TTF-1 is thought to be expressed specifically in pulmonary or thyroid neoplasms, and it is expressed in a significant subset of pulmonary non-small cell carcinomas, small cell carcinomas, and carcinoids but not in nonpulmonary, non-small cell carcinomas. Neuroendocrine tumors from sites other than the lung have not been evaluated for TFF-1 expression. We examined TFF-1 expression using immunohistochemistry on formalin-fixed, paraffin-embedded sections of 49 gastrointestinal carcinoids; 15 pancreatic islet cell tumors; 21 paragangliomas; 8 medullary thyroid carcinomas; 7 small cell carcinomas of the uterine cervix; 4 prostate, 4 bladder, and 6 Merkel cell (primary cutaneous neuroendocrine) carcinomas; and 1 renal carcinoma No gastrointestinal carcinoid tumor, pancreatic islet cell tumor, paraganglioma, or Merkel cell carcinoma expressed TFF-1. All of the medullary thyroid carcinomas strongly expressed TTF-1. However, 44% of nonpulmonary small cell carcinomas were also TTF-1 positive, including four of four prostate, two of four bladder, and one of seven cervical small cell carcinomas. We conclude that TTF-1 expression is not specific for small cell carcinomas of pulmonary origin and should not be used to distinguish primary from metastatic small cell carcinomas in extrapulmonary sites. However, TTF-1 expression may be useful in distinguishing Merkel cell carcinomas and cutaneous metastasis of small cell carcinomas. Among well-differentiated neuroendocrine tumors, TTF-1 expression seems to be present only in carcinoid tumors of the lung and medullary carcinomas of the thyroid and may be of differential diagnostic value when dealing with a metastatic well-differentiated neuroendocrine tumor.
authors.affiliation: Department of Pathology, University of Washington, Seattle, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Agoff
authors.forename: L W
authors.initials: LW
authors.lastname: Lamps
authors.forename: A T
authors.initials: AT
authors.lastname: Philip
authors.forename: M B
authors.initials: MB
authors.lastname: Amin
authors.forename: R A
authors.initials: RA
authors.lastname: Schmidt
authors.forename: L D
authors.initials: LD
authors.lastname: True
authors.forename: A L
authors.initials: AL
authors.lastname: Folpe
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors