Abstract

Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identifying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones.

Highlights

  • There are various types of thyroid cancers (TC), which are classified considering the cell of origin and histological characteristics into two main groups: a) well-differentiated, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Hürthle cell carcinoma; and b) poorly differentiated (PDTCs), such as anaplastic/undifferentiated thyroid carcinoma (ATC) and medullary thyroid cancer (MTC)

  • Vealed by immunohistochemistry that mortalin was increased in human MTC, papillary thyroid cancer (PTC), FTC, Immunohistochemistry, immunocytochemistry, and immunoblotting were used to and compared to normal thyroid tissues, suggesting a possible role of the chaperones assess the levels of the estrogen receptor alpha36 (ERα36), GRP78, and GRP94 in PTC

  • The immunohistochemical detection of Hsp70 showed that it was differentially localized in tumor cells, and that its nuclear translocation was correlated with the stage of the carcinogenic process and with prognosis: the nuclear translocation of the protein was found higher in samples with stage IV and with an unfavorable prognosis

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Summary

Thyroid Tumors

The thyroid nodules are benign, they are malignant in a small fraction of patients, representing cases of thyroid cancer (TC). There are various types of TC, which are classified considering the cell of origin and histological characteristics into two main groups: a) well-differentiated, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Hürthle cell carcinoma; and b) poorly differentiated (PDTCs), such as anaplastic/undifferentiated thyroid carcinoma (ATC) and medullary thyroid cancer (MTC). Despite the benefits of FNA cytology for diagnosing papillary, medullary, and anaplastic TC, it is not helpful in determining whether follicular or Hürthle cell thyroid growths are benign or malignant [4]. Approximately 10% of FNA results lead to misdiagnosis [5]. Other promising biomarkers are members of the chaperone system, whose role in thyroid carcinogenesis is still poorly understood

The Chaperone System
Quantitative Changes of Molecular Chaperones and Associated Effects in TC
Various Chaperones Assessed Simultaneously
Exosomes and TC
Conclusions and Perspectives for the Future
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