Papillary Thyroid Carcinoma: Molecular Distinction by MicroRNA Profiling.

Francesca Galuppini,Gianmaria Pennelli,Marta Sbaraglia,Isabella Merante Boschin,Federica Vianello,Luciano Cascione,Simona Censi,Nicola Valeri,Matteo Fassan,Marco Galasso,Massimo Rugge,Jens Claus Hahne,Loris Bertazza,Angelo Paolo Dei Tos,Susi Barollo,Giada Munari,Caterina Mian

doi:10.3389/fendo.2022.834075

Abstract

Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription–PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted.

Highlights

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, accounting for 80%– 90% of all tumors affecting this gland, and predominantly affects women [1, 2]
Nine classic variant (CV)-PTC cases were included as a control cohort
All cases of p.K601E-PTC resulted in a follicular variant (BRAF p.K601E FVPTC)

Summary

Introduction

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, accounting for 80%– 90% of all tumors affecting this gland, and predominantly affects women [1, 2]. Several factors have already been identified to be prognostic in the assessment of tumor aggressiveness such as age, gender, tumor size, pTNM, stage, and extrathyroid extension Of these prognostic factors, interest has focused on two particular variables: histological variants and molecular features. In addition to the classic morphology of PTC, more than 10 different histologic variants have been described Some of these can be distinguished solely based on a peculiar microscopic appearance, whereas others appear to have distinct clinical and prognostic characteristics. Hobnail PTC (HoV-PTC) has been recently identified as a rare but aggressive histological variant (about 0.2% of all PTCs) It typically is found at an advanced stage at the time of diagnosis and tends to develop in lymph nodes as distant metastases. Because of its low incidence and recent identification, further studies are needed to clearly define this variant from molecular, histological, and clinical points of view

Methods

Results

Conclusion