Abstract

BackgroundThe 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 resultsHere, 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).ConclusionsOur 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 slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8313753509421182

Highlights

  • Thyroid Transcription Factor-1(TTF-1), known as Nkx2.1 or thyroid-specific enhancer-binding protein, regulates genes in the thyroid, lungs, and diencephalon during embryogenesis [1,2]

  • 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

  • We recently documented a case of breast cancer with positive expression of TTF-1 [9], and we subsequently wanted to establish the frequency of TTF-1 expression in a population-based setting of breast cancer

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Summary

Introduction

Thyroid Transcription Factor-1(TTF-1), known as Nkx2.1 or thyroid-specific enhancer-binding protein, regulates genes in the thyroid, lungs, and diencephalon during embryogenesis [1,2]. TTF-1 has been regarded as a reliable marker for tumors originating in lung or thyroid tissues. Recent studies have demonstrated that this marker might be positive in some neuroendocrine tumors of different origins as well as in colorectal, gastric, endometrial, Regarding primary breast cancer, some cases with TTF-1 positivity have been reported [7,8,9,10,11] (Table 1). 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. Positive cases have recently been reported among primary breast carcinomas

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