Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases

Our plain-English summary of Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases, by M. Miettinen, Z. Wang, J. Lasota, et al (The American Journal of Surgical Pathology, 2015).

The study

• Authors: M. Miettinen, Z. Wang, J. Lasota, C. Heery, J. Schlom, C. Palena
• Journal: The American Journal of Surgical Pathology
• Published: 2015;39(10):1305-12
• Cited by: 106 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This laboratory study did not examine asbestos exposure. Pathologists at the National Cancer Institute stained 5229 tumor samples from anonymized surgical specimens, and normal adult and fetal tissues, with a new rabbit antibody against brachyury, a protein typical of chordoma. They counted only staining in cell nuclei, using a 1:2000 antibody dilution. All chordomas except one with sarcomatous change were positive (75/76), while chondrosarcomas of bone were negative. Positive results were common in embryonal carcinoma (25/34, 74%), seminoma (33/71, 46%) and small cell carcinoma of the lung (12/29, 41%). They were rare in lung adenocarcinoma (9/212), breast ductal carcinoma (1/427) and prostate adenocarcinoma (1/263). None of the 96 malignant mesotheliomas was positive, nor any colorectal, hepatocellular, renal, thyroid or squamous cell carcinoma. At lower antibody dilutions, breast cancers showed weak staining. The authors concluded that nuclear brachyury is a sensitive and fairly specific marker for chordoma, with reservations. They stated that the results depend on the antibody dilution and testing conditions used.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemical study of tumor tissue samples
• Who was studied: 5229 tumors from anonymized surgical specimens, arranged in multitumor blocks: chordomas plus 4119 carcinomas and other epithelial tumors (Table 1), and 1110 mesenchymal, neuroectodermal and lymphoid tumors (Table 2). Normal adult and fetal tissues were also studied. The work was done at the National Cancer Institute, Bethesda, MD.
• Exposure: No asbestos or other environmental exposure was studied. Tissues were stained with a rabbit monoclonal anti-brachyury antibody (MAb 54-1) at 1:2000 dilution, and only nuclear staining was scored.
• Main results:
  • All chordomas except one with spindle cell sarcomatous transformation showed nuclear brachyury (75/76, 99%).
  • Chondrosarcomas, including extraskeletal myxoid chondrosarcoma, lacked nuclear brachyury (bone chondrosarcoma 0/54).
  • Malignant mesothelioma: 0 of 96 cases showed nuclear brachyury.
  • Germ cell tumors: seminoma 33/71 (46%) and embryonal carcinoma 25/34 (74%) were positive. Embryonal carcinoma positivity was often focal.
  • Small cell carcinoma of the lung: 12/29 (41%) positive, the most frequently positive non-germ cell tumor.
  • Lung adenocarcinoma: 9/212 (4%) positive, usually with very focal labeling.
  • Breast ductal carcinoma: 1/427 (less than 1%) positive at the 1:2000 dilution.
  • Prostate adenocarcinoma: 1/263 (0.5%) positive.
  • All adrenocortical, colorectal, hepatocellular, renal, thyroid, ovarian serous and clear cell carcinomas were negative.
  • Among malignant mesenchymal and neuroectodermal tumors, only one case each of metastatic melanoma, malignant peripheral nerve sheath tumor, Ewing sarcoma, synovial sarcoma and embryonal rhabdomyosarcoma was positive. One follicular lymphoma was also positive.
  • In normal adult tissues, only scattered cells in seminiferous tubules showed nuclear brachyury.
  • At lower antibody dilutions (1:200 to 1:500), breast ductal carcinomas showed variably weak cytoplasmic and nuclear labeling.
• The authors' conclusion: The authors concluded that, with reservations, nuclear brachyury immunoreactivity is a sensitive and fairly specific marker for chordoma. They added that possible brachyury expression in non-chordoma tumors must be considered in diagnostic practice.
• Limitations the authors state:
  • Results depend on antibody dilution: lower dilutions give weak staining in other tumors such as breast and lung carcinomas.
  • Notochord tissue was not available in the fetal tissues examined.
  • The authors could not determine how brachyury-positive and brachyury-negative seminomas differ.

Topics

Medical terms in this study, explained in our Lexicon: Germ Cell Tumor, Carcinoma, Sarcoma, Immunohistochemistry, Monoclonal Antibody, Tubule, Adenocarcinoma, Squamous Cell.

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