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.

中文翻译：

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对 Fas 介导的细胞凋亡的抵抗与甲状腺乳头状癌中死亡受体的结构改变或表达变化无关

背景：恶性细胞对 FAS 介导的细胞死亡表现出显着的抵抗力，通过不同的过程，包括 FAS 突变、可溶性 FAS 表达或 P53 引起的 FAS 转录失调，最终逃避免疫监视。由于甲状腺癌被证明对 FAS 介导的细胞凋亡具有抗性，我们在甲状腺癌样本中研究了上述机制。方法：通过免疫组织化学分析了 37 个甲状腺癌样本的 FAS 外显子 9 和 TP53 外显子 5-8 的突变和蛋白质表达。此外，对甲状腺癌 mRNA 样本进行逆转录 - PCR，以评估跨膜 FAS 与其可溶形式的相对表达。结果：分析揭示了间变性癌中 TP53 突变的迹象，但在检查 TP53 或 FAS 外显子 9 突变的其他甲状腺标本中没有。在几乎所有甲状腺标本 (97%) 中观察到 FAS 受体表达，在乳头状癌中显着上调。仅在间变性癌中观察到 P53 核染色。在所有检查的样本中检测到全长 FAS mRNA，可溶性 FAS mRNA 要么不存在，要么含量非常低。结论：我们的结果表明，FAS 死亡域或 TP53 DNA 结合域突变、FAS 受体表达的下调或 FAS 可溶性同种型的表达与 FAS 介导的甲状腺乳头状癌细胞凋亡的表面抑制无关。在几乎所有甲状腺标本 (97%) 中观察到 FAS 受体表达，在乳头状癌中显着上调。仅在间变性癌中观察到 P53 核染色。在所有检查的样本中检测到全长 FAS mRNA，可溶性 FAS mRNA 要么不存在，要么含量非常低。结论：我们的结果表明，FAS 死亡域或 TP53 DNA 结合域突变、FAS 受体表达的下调或 FAS 可溶性同种型的表达与 FAS 介导的甲状腺乳头状癌细胞凋亡的表面抑制无关。在几乎所有甲状腺标本 (97%) 中观察到 FAS 受体表达，在乳头状癌中显着上调。仅在间变性癌中观察到 P53 核染色。在所有检查的样本中检测到全长 FAS mRNA，可溶性 FAS mRNA 要么不存在，要么含量非常低。结论：我们的结果表明，FAS 死亡域或 TP53 DNA 结合域突变、FAS 受体表达的下调或 FAS 可溶性同种型的表达与 FAS 介导的甲状腺乳头状癌细胞凋亡的表面抑制无关。