By NADIR R. FARID
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Additional info for Molecular Basis of Thyroid Cancer (Cancer Treatment and Research)
The results of these studies indicate that moderate to strong diffuse staining is confined to papillary carcinoma (Figure 11) whereas follicular neoplasms and hyperplastic nodules are negative or show only focal staining in areas of reaction to degeneration or previous fine needle aspiration biopsy. Nevertheless, only approximately 60% of papillary carcinomas are positive; a positive stain is therefore helpful, but negative stains are unable to assist in the diagnostic process. The diagnosis of this entity has been further advanced by the recognition of a family of gene rearrangements that are specific to papillary carcinoma (86).
The ret/PTC oncogenes (1 through 15, depending on the site of rearrangement, reviewed in (87)) are the result of DNA damage with rearrangements that transpose various cellular genes adjacent to the gene encoding the intracellular tyrosine kinase domain of the ret protooncogene (88–92). The rearrangements result in constitutive tyrosine kinase activation and translocation of the fusion protein to the cytoplasm (93). Animal models have shown the tumorigenicity of these fusion proteins (94–96); the rearrangements are common in radiation-induced tumors (97–101) but are also found in sporadic papillary carcinomas (102–105) and appear to be an early event in tumour development (106).
These lesion are distinguished from papillary carcinoma in that they are totally encapsulated, often show central cystic change, have subfollicle formation in the centres of broad oedematous papillae, and do not show nuclear features of papillary carcinoma (Figure 6). Although one analysis of clonality has suggested that these are polyclonal hyperplasias (56), the detection of or TSH receptor activating mutations in such nodules suggests that they are neoplasms (18–22). Their behaviour is almost always benign.
Molecular Basis of Thyroid Cancer (Cancer Treatment and Research) by NADIR R. FARID