Forty-six such nodules were analyzed for RET activation by immunohistochemistry and, in selected cases, by reverse transcriptase-polymerase chain reaction performed on RNA extracted after laser capture microdissection (LCM) of the tumor foci with and without papillary carcinoma features and positive RET immunoreactivity.
- To detect histologic and molecular differences separating NIFTP from follicular adenomas (FAs) and invasive carcinomas, particularly papillary carcinomas with extensive follicular growth (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV).
Therefore, the repression of CREB1 activity by CCDC6 has a critical function in the development of human thyroid papillary carcinomas carrying RET/PTC1 activation.
Chromosomal rearrangements involving the RET gene, known as RET/PTC, are prevalent in thyroid papillary carcinomas from patients with radiation history.
The identification of ret/PTC gene rearrangements refined the diagnosis of PC in 9 of 15 specimens (60%) that would otherwise have been considered indeterminate and in 2 of 6 that were considered insufficient for cytological diagnosis.
In fact, it has been demonstrated that: a) RET/PTC is an early event in the process of thyroid carcinogenesis and has a critical role in the generation of the papillary carcinoma; b) RET/PTC activation is essentially restricted to the papillary histotype and to the Hürthle thyroid tumors; c) its incidence increases after exposure to radiations.
We and others have shown that RET-PTC3 rearrangements are associated with the solid morphology seen in these short latency tumours, while classical papillary carcinomas more often show RET-PTC1 rearrangements.
Follicular variant of papillary carcinoma: reproducibility of histologic diagnosis and utility of HBME-1 immunohistochemistry and BRAF mutational analysis as diagnostic adjuncts.
Papillary carcinomas show frequently a specific gene rearrangement which gives rise to the formation of several types of so-called RET/PTC chimeric genes.
The identification of ret/PTC gene rearrangements refined the diagnosis of PC in 9 of 15 specimens (60%) that would otherwise have been considered indeterminate and in 2 of 6 that were considered insufficient for cytological diagnosis.
In this cohort, correlation between BRAF mutations and various clinicopathological parameters in 101 papillary carcinomas did not reveal any association with age at diagnosis, sex, tumour size, histological variants of PTC, multicentricity, cervical lymph node metastases, extrathyroidal invasion, distant metastases and clinical stage.
These data demonstrate that as opposed to the few reports on tumors arising after therapeutic external irradiation, ras mutations are not primary events in the development of post-Chernobyl thyroid papillary carcinomas. p53 mutations do not appear to be important in the development of these tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pediatric neoplasms.
The frequency, if we consider exclusively the papillary carcinomas, is in both cases 12%; (b) show that the TRK oncogene plays a role in the development of a minority of radiation-associated papillary thyroid carcinomas but not in adenomas; and (c) confirm that RET/PTC rearrangements are the major genetic alteration associated with ionizing radiation-induced thyroid tumorigenesis.
The present data do not support a major geographic difference in the prevalence of ret/PTC rearrangements in papillary carcinomas between Japan, the United States, and Italy.
For the sake of the discussion, well-differentiated carcinomas were divided into two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAFV600E mutations and RET/papillary thyroid carcinoma rearrangements and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPARγ rearrangement.
In summary, BRAFV600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAFV600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma.