Quantitative Immunomorphological Analysis of Heat Shock Proteins in Thyroid Follicular Adenoma and Carcinoma Tissues Reveals Their Potential for Differential Diagnosis and Points to a Role in Carcinogenesis

Alessandro Pitruzzella,Daniela Cabibi,Alessandra Vitale,Sabrina David,Alberto Fucarino,Francesca Rappa,Stefania Martorana,Fabio Bucchieri,Letizia Paladino,Calogero Cipolla,Alberto Macario,Everly Conway De Macario,Francesco Cappello,Giuseppa Graceffa

doi:10.3390/app9204324

Abstract

Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular carcinoma, comparing the tumor with the adjacent peritumoral tissue. Hsp60, Hsp70, and Hsp90 were increased in follicular carcinoma compared to follicular adenoma, while Hsp27 showed no difference. Histochemical quantification of Hsp60, Hsp70, and Hsp90 allows diagnostic distinction between follicular adenoma and carcinoma, and between tumor and adjacent non-tumoral tissue. The quantitative variations of these chaperones in follicular carcinoma suggest their involvement in tumorigenesis, for instance in processes such as invasion of thyroid parenchyma and metastasization.

Highlights

Thyroid tumors are the most frequent endocrine malignancies and their incidence is steadily increasing [1]
follicular adenoma (FA) is the most common benign thyroid tumor and occurs in follicular cells. It may appear as a single nodule, whose diameter can vary from a few millimetres to a few centimetres, surrounded by a single capsule. It is characterized by the proliferation of many follicles surrounded by a capsule and, depending on their size the adenomas can be sorted into normofollicular, microfollicular, macrofollicular, and solid-trabecular
We performed immunomorphological analysis on samples of FA and follicular carcinoma (FC) to evaluate, for the first time to our knowledge, the tissue levels of Hsp27, Hsp60, Hsp70, and Hsp90. We focused on these chaperones based on the fact that they are implicated in chaperonopathies, including carcinogenesis [15,19]

Summary

Introduction

Thyroid tumors are the most frequent endocrine malignancies and their incidence is steadily increasing [1]. They are divided into epithelial and non-epithelial tumors. FA is the most common benign thyroid tumor and occurs in follicular cells. It may appear as a single nodule, whose diameter can vary from a few millimetres to a few centimetres, surrounded by a single capsule. It is characterized by the proliferation of many follicles surrounded by a capsule and, depending on their size the adenomas can be sorted into normofollicular, microfollicular, macrofollicular, and solid-trabecular

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Conclusion