Skip to main content

The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas

Abstract

Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.

This is a preview of subscription content, access via your institution.

References

  1. Abutaily AS, Addis BJ, Roche WR: Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 55: 662–668, 2002.

    PubMed  Article  CAS  Google Scholar 

  2. Afify AM, Al-Khafaji BM: Diagnostic utility of thyroid transcription factor-1 expression in adenocarcinomas presenting in serous fluids. Acta Cytol 46: 675–678, 2002.

    PubMed  Google Scholar 

  3. Bejarano PA, Mousavi F: Incidence and significance of cytoplasmic thyroid transcription factor-1 immunoreactivity. Arch Pathol Lab Med 127: 193–195, 2003.

    PubMed  Google Scholar 

  4. Cai YC, Banner B, Glickman J, et al: Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol 32: 1087–1093, 2001.

    PubMed  Article  CAS  Google Scholar 

  5. Castro CY, Moran CA, Flieder DG, et al: Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases. Histopathology 39: 397–401, 2001.

    PubMed  Article  CAS  Google Scholar 

  6. Chhieng DC, Cangiarella JF, Zakowski MF, et al: Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens. Cancer 93: 330–336, 2001.

    PubMed  Article  CAS  Google Scholar 

  7. Fujita J, Ohtsuki Y, Bandoh S et al: Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines. Lung Cancer 39: 31–36, 2003.

    PubMed  Article  CAS  Google Scholar 

  8. Goldstein NS, Thomas M: Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies. Am J Clin Pathol 116: 319–325, 2001.

    PubMed  Article  CAS  Google Scholar 

  9. Gomez-Fernandez C, Jorda M, Delgado PI, et al: Thyroid transcription factor 1: a marker for lung adenoarinoma in body cavity fluids. Cancer 96: 289–293, 2002.

    PubMed  Article  CAS  Google Scholar 

  10. Haque AK, Syed S, Lele SM, et al: Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival. Appl Immunohistochem Mol Morphol 10: 103–109, 2002.

    PubMed  Article  CAS  Google Scholar 

  11. Hecht JL, Pinkus JL, Weinstein LJ, et al: The value of thyroid transcription factor-1 in cytologic preparations as a marker for metastatic adenocarcinoma of lung origin. Am J Clin Pathol 116: 483–488, 2001.

    PubMed  Article  CAS  Google Scholar 

  12. Jang KY, Kang MJ, Lee DG, et al: Utility of thyroid transcription factor-1 and cytokeratin 7 and 20 immunostaining in the identification of origin in malignant effusions. Anal Quant Cytol Histol 23: 400–404, 2001.

    PubMed  CAS  Google Scholar 

  13. Lau SK, Desrochers MJ, Luthringer DJ: Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases. Mod Pathol 15: 538–542, 2002.

    PubMed  Article  Google Scholar 

  14. Lau SK, Luthringer DJ, Eisen RN: Thyroid transcription factor-1: a review. Appl Immunohistochem Mol Morphol 10: 97–102, 2002.

    PubMed  Article  CAS  Google Scholar 

  15. Merchant SH, Amin MB, Tamboli P, et al: Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas. Am J Surg Pathol 25: 1515–1519, 2001.

    PubMed  Article  CAS  Google Scholar 

  16. Nakamura N, Miyagi E, Murata S, et al: Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod Pathol 15: 1058–1067, 2002.

    PubMed  Article  Google Scholar 

  17. Ng WK, Chow JC, Ng PK: Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens. Cancer 96: 43–48, 2002.

    PubMed  Article  CAS  Google Scholar 

  18. Ordonez NG: Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 24: 1207–1223, 2000.

    Google Scholar 

  19. Srodon M, Westra WH: Immunohistochemical staining for thyroid transcription factor-1: a helpful aid in discerning primary site of tumor origin in patients with brain metastases. Hum Pathol 33: 642–645, 2002.

    PubMed  Article  CAS  Google Scholar 

  20. Sturm N, Lantuejoul S, Laverriere MH, et al: E. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Hum Pathol 32: 918–925, 2001.

    PubMed  Article  CAS  Google Scholar 

  21. Wu M, Wang B, Gil J, et al: p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol 119: 696–702, 2003.

    PubMed  Article  Google Scholar 

  22. Yatabe Y, Mitsudomi T, Takahashi T: TTF-1 expression in pulmonary adenocarcinomas. Am J Surg Pathol 26: 767–773, 2002.

    PubMed  Article  Google Scholar 

  23. Zamecnik J, Kodet R: Value of thyroid transcription factor-1 and surfactant apoprotein A in the differential diagnosis of pulmonary carcinomas: a study of 109 cases. Virchows Arch 440: 353–361, 2002.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judit Moldvay MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Moldvay, J., Jackel, M., Bogos, K. et al. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol. Oncol. Res. 10, 85–88 (2004). https://doi.org/10.1007/BF02893461

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02893461

Keywords

  • TTF-1
  • immunohistochemistry
  • lung adenocarcinoma
  • metastasis