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Updated: Feb 4, 2026
Transoral Robotic Total Thyroidectomy and Bilateral Central Regional Lymph Node Dissection for Papillary Thyroid Carcinoma
Published on: September 15, 2023
Resistance to Fas-Mediated Apoptosis Does Not Correlate to Structural Alterations or Expression Changes of the Death
1, Angelica A Saetta2, Andreas C Lazaris2
1First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greecegfanourak@med.uoa.gr.
Background:
Malignant cells exhibit significant resistance to FAS-mediated cell death, through different processes, including FAS mutations, soluble FAS expression, or FAS transcriptional dysregulation by P53, eventually escaping from immune surveillance. Since thyroid carcinomas were shown to be resistant to FAS-mediated apoptosis, we investigated the above mechanisms in thyroid carcinoma samples.
Methods:
Thirty-seven thyroid carcinoma samples were analyzed for mutations in FAS exon 9 and TP53 exons 5-8 and protein expression by means of immunohistochemistry. Moreover, thyroid carcinoma mRNA samples were subjected to reverse transcription - PCR, to evaluate the relative expression of transmembrane FAS versus its soluble form.
Results:
Analysis revealed indications for TP53 mutations in the anaplastic carcinomas, but not in the other thyroid specimens examined for TP53 or FAS exon 9 mutations. FAS receptor expression was observed in almost all thyroid specimens (97%) with significant up-regulation in papillary carcinomas. P53 nuclear staining was observed only in anaplastic carcinomas. Full-length FAS mRNA was detected in all specimens examined, with soluble FAS mRNA being either absent or present in very low amounts.
Conclusions:
Our results denote that FAS death domain or TP53 DNA-binding domain mutations, down-regulation of FAS receptor expression, or expression of FAS soluble isoform are not responsible for the seeming inhibition of FAS-mediated apoptosis in papillary thyroid carcinoma cells.
Insights
Thyroid carcinomas resist FAS-mediated cell death. Researchers found no FAS or TP53 mutations, nor soluble FAS expression, explaining this resistance in papillary thyroid cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Malignant cells resist FAS-mediated cell death via mutations, soluble FAS, or P53 dysregulation, evading immune surveillance.
- Thyroid carcinomas exhibit resistance to FAS-mediated apoptosis, necessitating investigation into underlying mechanisms.
Purpose of the Study:
- Investigate mechanisms of FAS-mediated apoptosis resistance in thyroid carcinoma samples.
- Analyze FAS and TP53 mutations, and FAS expression in thyroid carcinomas.
Main Methods:
- Analyzed 37 thyroid carcinoma samples for FAS exon 9 and TP53 exons 5-8 mutations.
- Assessed protein expression via immunohistochemistry and mRNA levels of transmembrane vs. soluble FAS using RT-PCR.
Main Results:
- TP53 mutations were indicated in anaplastic carcinomas only; no FAS or TP53 mutations found in other types.
- FAS receptor expression was high in most samples (97%), notably up-regulated in papillary carcinomas.
- Full-length FAS mRNA was ubiquitous; soluble FAS mRNA was absent or minimal.
Conclusions:
- FAS death domain or TP53 DNA-binding domain mutations do not cause FAS-mediated apoptosis inhibition.
- Down-regulation of FAS receptor expression is not responsible for apoptosis resistance.
- Soluble FAS isoform expression does not explain the observed inhibition of FAS-mediated apoptosis in papillary thyroid carcinoma cells.
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