Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors

Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcripti on factor that is expressed in the developing thyroid, respiratory epitheli um, and diencephalon. TTF-1 is thought to be expressed specifically in pulm onary 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, nonsmall cell carcinomas. Neuroendocrine tumors fr om sites other than the lung have not been evaluated for TTF-1 expression. We examined TTF-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 sm all cell carcinomas of the uterine cenvix; 4 prostate, 4 bladder, and 6 Mer kel cell (primary cutaneous neuroendocrine) carcinomas; and 1 renal carcino ma No gastrointestinal carcinoid tumor, pancreatic islet cell tumor, paraga nglioma, or Merkel cell carcinoma expressed TTF-1. All of the medullary thy roid carcinomas strongly expressed TTF-1. However, 44% of nonpulmonary smal l 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 metast atic small cell carcinomas in extrapulmonary sites. However, TTF-1 expressi on may be useful in distinguishing Merkel cell carcinomas and cutaneous met astasis of small cell carcinomas. Among well-differentiated neuroendocrine tumors, TTF-1 expression seems to be present only in carcinoid tumors of th e lung and medullary carcinomas of the thyroid and may be of differential d iagnostic value when dealing with a metastatic well-differentiated neuroend ocrine tumor.