ABSTRACT
RET/PTC oncogene expression is restricted to papillary thyroid carcinomas (PTC). At least three forms of this oncogene have been described. These are generated by the rearrangement of the 5'-terminal region of different expressed genes with the tyrosine-kinase (TK) domain of the ret proto-oncogene. Several studies showing the correlation between the expression of this oncogene, clinical outcome, and histological subtypes have been published. Thirty-five paraffin-embedded PTC samples from patients without a history of radiation exposure were studied. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to determine a possible correlation between RET activation, clinical outcome, and tumor subtype. Almost half of the studied cases presented with tumoral extension or metastases. Ret gene transcripts and protein were found in all PTC variants as well as in their corresponding metastases. In contrast, none of the follicular adenomas, goiters, or normal follicular cells from the thyroid gland showed evidence of ret activation. We observed a high frequency of ret expression in PTCs, suggesting that ret activation is a common event in nonradiation-related PTC from Mexican patients.
Subject(s)
Carcinoma, Papillary/enzymology , Drosophila Proteins , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Thyroid Neoplasms/enzymology , Adult , Carcinoma, Medullary/chemistry , Carcinoma, Papillary/chemistry , Carcinoma, Papillary/genetics , Enzyme Activation , Female , Gene Expression , Humans , Immunohistochemistry , In Situ Hybridization , Male , Mexico , Middle Aged , Proto-Oncogene Mas , Proto-Oncogene Proteins/analysis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-ret , Receptor Protein-Tyrosine Kinases/analysis , Receptor Protein-Tyrosine Kinases/genetics , Thyroid Neoplasms/chemistry , Thyroid Neoplasms/geneticsABSTRACT
The dominantly inherited Multiple Endocrine Neoplasia cancer syndrome type 2B (MEN2B) is characterized by the presence of medullary thyroid carcinoma (MTC), phaechromocytoma (PHAEO), mucosal neuromas, ganglioneuromas of the intestinal tract, skeletal and ophthalmic abnormalities. MEN2B has been associated with a specific point mutation in the tyrosine kinase domain of the RET proto-oncogene (918RET mutation). We investigated a Mexican patient MEN2B for the presence of the 918RET mutation using the polymerase chain reaction followed by restriction endonuclease digestion. We have detected this mutation in DNA from the patient's MTC, PHAEO, and peripheral blood cells, but not in DNA from the patient's mother, suggesting that this mutation arose de novo. Our results are in agreement with the suggestion that the 918RET mutation is present in a vast majority of MEN2B cases around the world.
