Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites

Histopathology. 2000 May;36(5):415-20. doi: 10.1046/j.1365-2559.2000.00890.x.


Aims: The thyroid transcription factor-1 (TTF-1) is a highly specific immunohistochemical marker for the identification of pulmonary adenocarcinomas and non-neuroendocrine large cell carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site. In this study we tested if anti-TTF-1 can also be used to verify a pulmonary origin of neuroendocrine carcinomas, placing emphasis on the discrimination of pulmonary small cell carcinomas (SCCs) from extrapulmonary SCCs and the distinction of SCCs from Merkel cell carcinomas of the skin.

Methods and results: We studied 37 pulmonary SCCs, 15 SCCs of extrapulmonary origin, 4 pulmonary large cell neuroendocrine carcinomas (LCNECs), four extrapulmonary LCNECs, six medullary thyroid carcinomas, 16 Merkel cell carcinomas, and a total of 32 carcinoids/low-grade neuroendocrine carcinomas of pulmonary (12 cases) and extrapulmonary (20 cases) origin. Using the commercially available monoclonal antibody 8G7G3/1, TTF-1 was immunohistochemically detectable in 81% of pulmonary SCCs but also in 80% of extrapulmonary SCCs. Furthermore, anti-TTF-1 showed a positive staining in 50% of all pulmonary carcinoids, in one gastric carcinoid, in 2/4 of pulmonary, and 1/4 of extrapulmonary LCNECs. All medullary thyroid carcinomas were also TTF-1-positive. Merkel cell carcinomas were consistently TTF-1-negative.

Conclusions: Our results suggest that in contrast to non-neuroendocrine carcinomas, anti-TTF-1 cannot be used to prove or to exclude a pulmonary origin of SCCs or LCNECs of unknown or uncertain primary site. Therefore, before using anti-TTF-1 as a marker for pulmonary carcinomas one should be sure to have excluded SCC and LCNEC. On the other hand, anti-TTF-1 might be used to specifically discriminate SCCs of various origin from Merkel cell carcinomas.

MeSH terms

  • Antibodies, Monoclonal
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Merkel Cell / metabolism*
  • Carcinoma, Merkel Cell / pathology
  • Carcinoma, Small Cell / metabolism*
  • Carcinoma, Small Cell / pathology
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Nuclear Proteins / metabolism*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism*


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