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Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomas

Tor A Klingen1*, Ying Chen1, Pål Suhrke1, Ingunn M Stefansson34, Marian D Gundersen2 and Lars A Akslen34

Author affiliations

1 Department of Pathology, Vestfold Hospital Trust, Tønsberg, Norway

2 Department of Radiology, Vestfold Hospital Trust, Tønsberg, Norway

3 Centre for Cancer Biomarkers, The Gade Institute, University of Bergen, Bergen, Norway

4 Department of Pathology, Haukeland University Hospital, Bergen, Norway

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Citation and License

Diagnostic Pathology 2013, 8:80  doi:10.1186/1746-1596-8-80

Published: 15 May 2013



The differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas.

Methods and results

Here, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population-based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong) was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03).


Our population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors.

Virtual slides

The virtual slide(s) for this article can be found here: webcite

Thyroid transcription factor-1; Breast cancer; Basal-like phenotype; Adverse prognostic factors