Genetic events in the evolution of thyroid cancer.
OBJECTIVE
To delineate the evolution of thyroid cancer using the Volgelstein model of cancer evolution and to demonstrate the genetic "hits" in the development of undifferentiated cancer from normal thyroid cells.


METHODS
Immunohistochemical and molecular biologic techniques were used to delineate the prevalence of (1) the ras oncogene, (2) p53, and (3) the ret/PTC oncogene in the development of differentiated thyroid cancer from normal cells and hyperplasia. The evolution of differentiated thyroid cancer to the dedifferentiated or anaplastic type was also investigated. The methodology used was standard immunohistochemical staining techniques as well as polymerase chain reaction technology for the elucidation of these various oncogenes and tumour suppressor genes.


RESULTS
We have demonstrated that there is a high preponderance of ras and ret/PTC oncogenes in the evolution of thyroid cancer. Further along the continuum, p53 has been demonstrated to be prevalent in the development of dedifferentiated thyroid cancer (i.e., tall cell and insular variety as well as anaplastic cancer).


CONCLUSIONS
Several genetic hits have been demonstrated to be prevalent in the evolution of thyroid cancer. These are preliminary oncogenic maps, and further work in this area will help to establish a definite biologic pattern in the development of this malignancy.
Freeman
Jeremy
J
Department of Otolaryngology, Mount Sinai Hospital, Toronto, Ontario.
Carroll
Camilla
C
Asa
Sylvia
S
Ezzat
Shereen
S
D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D015321:Gene Rearrangement; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human