Chordoma is a rare cancer that universally over expresses brachyury
and occurs in the base of the skull and spine.
In the case of cardiomyocytes, brachyury
, a-cardiac actin, atrial natriuretic factor and the specific sarcomeric myosin heavy chain (clone MF20) expression could be applied as markers of mature cardiomyocytes.
Most chordomas present high levels of expression of brachyury
, a key transcription factor for the development of notochord, being silenced after embryonic development.
The following markers were used to determine differentiation efficiency: brachyury
(R&D Systems) for mesoendoderm, Nkx2.5 (Abcam) for cardiac mesoderm, Nkx2.5 and Isl1 (Developmental Studies Hybridoma Bank) for cardiac progenitors, cTnT (Thermo Fisher Scientific) for cardiomyocytes, double staining of FOXA2 (GeneTex) and SOX17 (GeneTex) for endoderm, CDX2 (GeneTex) for mid/hindgut, Otx2 (R&D Systems) for day 5 neural induction, and PAX6 (GeneTex) for neuroepithelium [17-20].
The tumor cells are typically immunoreactive for cytokeratins, EMA, S100 protein, and Brachyury
, with the latter being highly specific (Figure 12, A through D).
Several findings appear to support the theory of a common ancestry, including the fact that the stromal cells express some proteins (stem cell leukemia, brachyury
) characteristic of embryonic progenitor cells with hemangioblastic differentiation potential .
Earliest cardio-myogenesis is linked with a peak in the expression of primitive streak, mesoderm, and cardiomesoderm markers like Brachyury
and MESP1 at 7 days of differentiation.
In addition to immunotherapy, vaccines are being evaluated in the adjuvant setting for pancreatic cancer; 5-Fluorouracil (5-FU)-based chemoradiation combined with a pancreatic cancer vaccine of irradiated granulocyte-macrophage colony stimulating factor (GM-CSF) is undergoing clinical trials, and a vaccine was recently developed against the mesenchymal-associated transcription factor brachyury
, which is currently undergoing clinical trials for the treatment of solid tumors .
"We herein report an exceptional case of extra-axial dedifferentiated chordoma confirmed by the expression of brachyury
, the first case report of this kind," reported surgical pathologist Dr.
It is important to note that in recent and improved studies, other markers were found to identify definitive endoderm, including Sox17, Brachyury
protein, CXC-chemokine receptor type 4, and Cerberus (73).
A prominent example of this coordination is found in the gastrulation of amniotes, where Brachyury
(Bra), a transcription factor, is synchronously and transiently expressed in a localized population, the Primitive Streak (PS).
ZicL directly binds to an enhancer of Brachyury
, (63) which encodes a key transcription factor for differentiation of the notochord, and this binding confers competence for FGF induction on this gene.