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

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

TTF-1 positive breast cancer: a cautionary tale

“…TTF-1 positivity has been reported in several histological subtypes, including invasive ductal,2–5 invasive lobular,2 3 medullary4 and small cell carcinoma 6. A population-based study featuring seven positive cases suggested that TTF-1 expression is significantly associated with grade 3 tumours and ‘triple negative’ (ER, PR and HER2 negative) disease,3 a phenotype consistent with our case.…”

“…There are very few reports of TTF-1 positive breast cancer in the literature, although small population-based studies have estimated that up to 2.8% of primary breast cancers may express TTF-1 at least weakly or focally 2 3. TTF-1 positivity has been reported in several histological subtypes, including invasive ductal,2–5 invasive lobular,2 3 medullary4 and small cell carcinoma 6.…”

Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survival

“…CK5/6 and/or P-cadherin positivity was used to define basal-like differentiation,16 17 and for these markers, cases were evaluated for intensity of staining and expression area. A staining index (values 0–9), obtained as a product of staining intensity (0–3) and proportion of immunopositive tumour cells (≤10%=1, 10–50%=2, >50%=3) were calculated.…”

Diagnostic challenge in a metastatic pulmonary adenocarcinoma with neuroendocrine differentiation to breast and skin

“…Although, TTF1 shows high degree of infidelity in terms of the origin of a neuroendocrine carcinoma and does not essentially correlate with its pulmonary origin, it can safely be used as a marker of metastatic NET . However, about 4% of mammary carcinomas can express TTF1 . For practical purpose, we corroborated TTF1 positivity with the pulmonary origin of the tumor.…”