Author:
Máximo Valdemar,Lima Jorge,Prazeres Hugo,Soares Paula,Sobrinho-Simões Manuel
Abstract
The biology and the genetics of Hürthle cell tumors are reviewed starting from the characterization and differential diagnosis of the numerous benign and malignant, neoplastic and nonneoplastic lesions of the thyroid in which Hürthle cell transformation is frequently observed. The clinicopathologic and molecular evidence obtained from the comparative study of the aforementioned conditions indicate that Hürthle cell appearance represents a phenotype that is superimposed on the genotypic and conventional histopathologic features of the tumors. Hürthle cell tumors differ from their non-Hürthle counterparts regarding the prevalence of large deletions of mitochondrial DNA (mtDNA), mutations of mtDNA genes coding for oxidative phosphorylation (OXPHOS) proteins (namely mutations of complex I subunit genes) and mutations of nuclear genes coding also for mitochondrial OXPHOS proteins. Such mitochondrial alterations lead to energy production defects in Hürthle cell tumors; the increased proliferation of mitochondria may reflect a compensatory mechanism for such defects and is associated with the overexpression of factors involved in mitochondrial biogenesis. The mitochondrial abnormalities are also thought to play a major role in the predisposition for necrosis instead of apoptosis which seems to be blocked in most Hürthle cell tumors. Finally, the results obtained in experimental models using cybrid cell lines and the data obtained from histopathologic and molecular studies of familial Hürthle cell tumors are used, together with the aforementioned genetic and epigenetic alterations, to progress in the understanding of the mechanisms through which mitochondrial abnormalities may be involved in the different steps of thyroid carcinogenesis, from tumor initiation to metastization.
Subject
Cancer Research,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Cited by
72 articles.
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