Brachyury is a
transcription factor of the T-box family typically expressed in notochord and
chordoma. Some studies report
brachyury as highly specific for
chordoma, whereas others have concluded that
brachyury is expressed in many types of common
carcinomas by reverse transcription polymerase chain reaction and immunohistochemistry and could be involved in the epithelial-mesenchymal transition and metastatic process. In this study, we immunohistochemically evaluated 5229 different
tumors for nuclear
brachyury expression using a new rabbit
monoclonal antibody and automated immunostaining (Leica Bond Max). Only nuclear labeling was scored, and antibody dilution of 1:2000 was used. In normal tissues, only rare cells in seminiferous tubules were labeled; all other organs were negative. All
chordomas (75/76), except a sarcomatous one, were positive, whereas
chondrosarcomas were negative. Among epithelial
tumors, positivity was often detected in
embryonal carcinoma (74%) and
seminoma (45%). Pulmonary
small cell carcinoma was often positive (41%), whereas pulmonary and pancreatic
adenocarcinomas only rarely showed nuclear
brachyury positivity (3% to 4%). Common
carcinomas such as
ductal carcinomas of the breast or
adenocarcinomas of the prostate only exceptionally showed nuclear positivity (<1%). No colorectal, hepatocellular, renal cell, squamous cell, thyroid or urothelial
carcinoma, or
mesothelioma showed nuclear
brachyury positivity. Among mesenchymal and
neuroectodermal tumors, only isolated cases of
melanoma, malignant peripheral nerve sheath tumor,
rhabdomyosarcoma,
synovial sarcoma, and
follicular lymphoma showed nuclear expression. However, as shown previously with lung
carcinoma, experiments with lower antibody dilutions (1:200 to 1:500) showed weak cytoplasmic and nuclear labeling in breast
cancers. In addition to
chordoma, we show here for the first time that nuclear
brachyury expression is prevalent in
embryonal carcinoma,
seminoma, and
small cell carcinoma of the lung but very rare in common
carcinomas,
sarcomas, and
melanoma. With these reservations, we have demonstrated the presence of nuclear
brachyury immunoreactivity to be a sensitive and fairly specific marker for
chordoma.