Histological Study of Chordoma Origin From Fetal Notochordal Cell Rests

Study Design. The histological comparative study was performed on chordoma and notochordal cell rests (NCRs). Objective. To understand the histological similarity and homology of chordoma and NCRs, further supplying direct evidence of chordoma origin from NCRs. Summary of Background Data. Although many studies supported the hypothesis that chordoma arise from NCRs, there has been little direct evidence reported to date. Of the base of our previous study, we conducted a comparative histological study among NCRs coexisting in chordoma, fetal NCRs, and chordoma tumor components. Methods. Thirty fetal nucleus pulposus and 46 chordoma specimens were harvested, and classic chordoma tumor markers and brachyury expression levels were investigated through immunohistochemical method. Results. The fetal NCRs existed in the form of clusters in the center of nucleus pulposus <36 gestational weeks; NCRs coexisting in chordoma specimens consisted of packed cells without extracellular myxoid matrix. Both the above-mentioned NCRs as well as chordoma tumor components showed high sensitivity for classic chordoma tumor makers (epithelial membrane antigen, AE1/AE3, CAM5.2, vimentin, S-100); both kinds of NCRs showed completely negative expression for brachyury, whereas chordoma tumor components demonstrated 100% positivity. Conclusion. Our study results supported histological similarity and homology of NCRs coexisting in chordoma and in fetal nucleus pulposus. Brachyury activation probably takes an important role in chordoma tumoregenesis.