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

Mod Pathol. 2000 Mar;13(3):238-42. doi: 10.1038/modpathol.3880044.


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.

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Carcinoma, Medullary / metabolism*
  • Carcinoma, Medullary / pathology
  • Carcinoma, Small Cell / metabolism*
  • Carcinoma, Small Cell / pathology
  • Female
  • Fluorescent Antibody Technique, Direct
  • Humans
  • Male
  • Neoplasm Proteins / biosynthesis
  • Nuclear Proteins / biosynthesis*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / biosynthesis*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor
  • NKX2-1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors