The Sonic Hedgehog Signaling and Its Components in Recurrent Chordoma of the Spine

Abstract

Chordomas are uncommon primary malignant tumours that have a high rate of recurrence. They are thought to form along the spine from remains of the embryonic notochord. Treatment for recurrent tumours is complicated and contentious.

They are unresponsive to conventional chemotherapy and radiotherapy. Chordomomas simply lack a viable chemotherapeutic standard. Throughout the fetus's development, the Sonic Hedgehog (SHH) pathways connecting a variety of processes involved in tissue and organ expansion and differentiation. To investigate the role of signalling the hedgehog in recurrent spinal chordomas, immunohistochemistry was used to identify SHH and GLI1 levels. In situ hybridization was also used to differentiate PTCH1 and GLI1 expressions.

Methods

From 1997 to 2020, we looked at 23 paraffin-embedded recurrent spinal chordoma samples from 23 patients (9 men, 14 women; median age: 63 years). All the patients were treated at the University Medical Center Goettingen in Germany and Azad University of Medical Sciences in Tehran, Iran. This study only included patients who had been diagnosed with conventional chordoma.

Results

SHH expression (+) and GLI1 expression were discovered in all 23 cases (+) immunohistochemically. GLI1 and SHH levels were markedly increased by recurrent spinal chordoma scores. In the recurrent spinal chordoma, in situ hybridization demonstrated positive responses for PTCH1 and GLI1.

Conclusion

The Shh sample that represents is believed to play a role in spinal chordoma recurrence.

The increased amounts of SHH and GLI1 activity in all chordoma samples, according to the study, indicate an autocrine ligand-dependent activation of the conventional HH signalling cacade. It's hard to rule out a non-canonical or paracrine pathway. Hedgehoginhibitors, such as SHH- and GLI-inhibitors, are believed to be associated in our findings, could be a promising approach for treating recurrent spinal chordomas.