Three-dimensional telomere profiles in papillary thyroid cancer variants: A pilot study.

Aline Rangel-Pozzo,Roberta Vanni,John Gartner,Paola Caria,Tinuccia Dettori,Garbor Fisher,Federica Etzi,Daniela Virginia Frau,Sabine Mai

doi:10.17305/bjbms.2021.6639

Abstract

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

Highlights

In the present pilot study, we examined fifteen formalin-fixed paraffin-embedded (FFPE) thyroid neoplasms comprising classical papillary thyroid carcinoma (CL-PTC) (n=4), follicular variant PTC (FV-PTC) (n=3), NIFTP (n=4), and follicular thyroid adenoma FTA (n=4)
No significant differences were observed between FTA and NIFTP or between classical PTC (CL-PTC) and FV-PTC, NIFTP paralleling FTA telomere length while having longer telomeres compared to CL-PTC and FV-PTC
The analysis of the 3D telomere profiles in normal adjacent tissue (NAT) showed that most of the telomere parameters were different between NAT and FTA tumor area and NAT and NIFTP tumor area, whereas number of telomeres signals and total intensity were significantly different between NAT and CL-PTC tumor area, and the average intensity was different between NAT and FV-PTC (Table 2)

Summary

Introduction

Thyroid cancer is one of the most common malignant endocrine neoplasms, and papillary thyroid carcinoma (PTC) constitutes approximately 80% of all thyroid cancer cases [1]. The Cancer Genome Atlas (TCGA) study [2] has demonstrated a strong correlation between genetic alterations and histologic phenotypes of thyroid neoplasia, resulting in the identification of two distinct molecular subgroups: the BRAFV600E-like nodules, which show the true papillary architecture, and RAS-like nodules, with a follicular-pattern that includes follicular thyroid adenoma (FTA), follicular carcinoma, and follicular variant PTC (FV-PTC). Harmful outcomes can occur that alter the three-dimensional (3D) nuclear telomere and genome organization in cancer cells [9] On these bases, considering that the biological features of NIFTP are still unclear, possibly due to the highly variable incidence (

Methods

Results

Conclusion