Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy

Abstract

Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.

Can We Predict Differentiated Thyroid Cancer Behavior? Role of Genetic and Molecular Markers

“…It is expressed in normal thyroid tissue and benign lesions, while its expression reduces with the progression of differentiated TC towards undifferentiated ones. Loss of E-Cadherin expression is noticed in the majority of anaplastic thyroid cancers [ 5 , 140 , 141 , 142 , 143 , 144 , 145 ].…”

“…The increased expression has been reported in various epithelial cancers, including gastrointestinal tumors, prostate cancer, breast cancer, CNS tumors, TC, etc. The exact role of vimentin in cancer progression remains unclear, but increased expression could be associated with increased tumor growth, invasion, and poor prognosis [ 5 , 137 ]. In adults, vimentin expression is limited to connective tissue mesenchymal cells, muscle cells, and CNS [ 149 ].…”

“…These processes are mediated directly or indirectly through numerous secondary molecule derangements. Activation and further cooperation of genes and molecules, along with the interaction between the tumor and its surrounding environment, are core aspects of the development and progression of DTC [ 3 , 4 , 5 ].…”

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine

“…The classical variant presents typical microscopic features ( Figure 5 A), such as overlapping and clearing nuclei, irregularities of nuclear membrane in papillary architecture with fibrovascolar cores, psammoma bodies and sometimes aggregates of lymphocytes. Sixteen PTC variants with different behavior have been reported so far [ 81 , 82 , 83 , 84 , 85 , 86 ]. After the classic variant, the most common variants are the follicular one ( Figure 5 B), hobnail/micropapillary ( Figure 5 C), Whartin-like ( Figure 5 D) and solid one [ 81 , 82 , 83 ].…”

“…After the classic variant, the most common variants are the follicular one ( Figure 5 B), hobnail/micropapillary ( Figure 5 C), Whartin-like ( Figure 5 D) and solid one [ 81 , 82 , 83 ]. In spite of this morphological variability, molecular ITH is not constantly present, even in multifocal PTCs [ 84 , 85 , 86 ].…”