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.
Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients.
As such, this article addresses the following aspects of intragenic mutations in thyroid cancer: thyroid stimulating hormone receptor and guanine-nucleotide-binding proteins of the stimulatory family mutations in hyperfunctioning tumors; mutations in RAS and other genes and aneuploidy; PAX8-PPARgamma rearrangements; BRAF mutations; mutations in oxidative phosphorylation and Krebs cycle genes in Hürthle cell tumors; mutations in succinate dehydrogenase genes in medullary carcinoma and C-cell hyperplasia; and mutations in TP53 and other genes in poorly differentiated and anaplastic carcinomas.
It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas.
We found higher incidence of p53 mutation and aberrant processing of FHIT mRNA in malignant tumors (papillary, follicular, medullary and anaplastic carcinomas) and in those tumors with distant metastasis.
These facts indicate that an N-ras mutation may induce follicular neoplasm and a subsequent p53 mutation may have caused the follicular neoplasm to transform to anaplastic carcinoma in this patient.
Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas.
Considering that TCIC is intermediate between papillary plus follicular carcinoma and anaplastic carcinoma in terms of survival and the rate of mutation of the p53 gene, we can speculate that mutation in the p53 gene might be associated with the insular component and might play an important role in the clinicopathological behavior of thyroid carcinoma.
Ras point mutations are frequently observed in tumors with follicular histology and a high prevalence of p53 point mutations have been found in anaplastic carcinomas.
Formalin fixed, paraffin wax embedded tissues from four cases of anaplastic carcinomas associated with thyroid papillary carcinomas were studied by immunohistochemistry with two different p53 monoclonal antibodies.
cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene.
In spite of the marked increase in the expression of oncofetal fibronectin mRNA with the IIICS sequence in papillary and anaplastic carcinomas in the previous reports, the relative expression levels of each splice variant with or without the IIICS sequence showed no difference among all the tumor types.
These results suggest the possibility of establishing a more accurate preoperative or postoperative diagnosis of papillary and anaplastic carcinomas by measuring the relative expression level of oncofetal fibronectin to thyroglobulin in thyroid tumors.
This result encourages us to establish gene diagnosis of thyroid papillary and anaplastic carcinomas by detecting oncofetal fibronectin mRNA in biopsies.
The expression of oncofetal fibronectin mRNA in benign and malignant tissues was examined by Northern blot and reverse transcription-PCR using specific primers of its cDNA sequence, and its increased expression was observed only in papillary and anaplastic carcinomas.