ArticlePloS one2019
New insights into intranuclear inclusions in thyroid carcinoma: Association with autophagy and with BRAFV600E mutation.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 17 citations in OpenAlex.
- Response to the letter to the editor: Appraisal of suspicious for malignancy cytology: nuclear characteristics deserve special attention in reported cytology analysis - real-world scenario cohort in thyroidology.Archives of endocrinology and metabolism · 2026Article
- Deep Invaginations of Nuclear Envelope Coordinate Spatial Organization of Chromatin in Epithelium.bioRxiv : the preprint server for biology · 2026Article
- Diagnostic Performance of Ultrasonography Compared to Cross-Sectional Imaging in Thyroid-Related Nodal Metastasis: A Retrospective Cohort Study from Saudi Arabia.Cancer management and research · 2026Article
- Altered expression of autophagy-related molecules and β-catenin in different subtypes of thyroid cancer: co-localization in intranuclear cytoplasmic inclusions.Endocrine journal · 2025Article
- In suspicious for malignancy thyroid nodule aspirates, nuclei characteristics deserves special attention in reported cytology analysis - real world scenario cohort.Archives of endocrinology and metabolism · 2025Article
- Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes.Journal of pathology and translational medicine · 2024Review
- Three-dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block-face scanning electron microscopy (SBF-SEM).Pathology international · 2023Article
- Black thyroid: a note for the surgeon, the pathologist and the dermatologist.Gland surgery · 2023Article
- The Presence of Typical "BRAFV600E-Like" Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation.Endocrine pathology · 2023Article
- A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model.Endocrine pathology · 2022Article
- Characterization of two types of intranuclear hepatocellular inclusions in NAFLD.Scientific reports · 2020Article
- Diagnostic Utility of p62 Expression in Intranuclear Inclusions in Thyroid Core Needle Biopsy Specimens.In vivo (Athens, Greece)Article
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Authors and funding
11 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundIntranuclear inclusions (NI) in normal and neoplastic tissues have been known for years, representing one of the diagnostic criteria for papillary thyroid carcinoma (PTC). BRAF activation is involved among others in autophagy. NI in hepatocellular carcinoma contain autophagy-associated proteins. Our aim was to clarify if NI in thyroid carcinoma (TC) have a biological function.
methodsNI in 107 paraffin-embedded specimens of TC including all major subtypes were analyzed. We considered an inclusion as positive if it was delimited by a lamin AC (nuclear membrane marker) stained intact membrane and completely closed. Transmission electron microscopy (TEM), immunohistochemistry (IHC), immunofluorescence (IF) and 3D reconstruction were performed to investigate content and shape of NI; BRAFV600E mutation was analyzed by next generation sequencing.
resultsIn 29% of the TCs at least one lamin AC positive intranuclear inclusion was detected; most frequently (76%) in PTCs. TEM analyses revealed degenerated organelles and heterolysosomes within such NI; 3D reconstruction of IF stained nuclei confirmed complete closure by the nuclear membrane without any contact to the cytoplasm. NI were positively stained for the autophagy-associated proteins LC3B, ubiquitin, cathepsin D, p62/sequestosome1 and cathepsin B in 14-29% of the cases. Double-IF revealed co-localization of LC3B & ubiquitin, p62 & ubiquitin and LC3B & p62 in the same NI. BRAFV600E mutation, exclusively detected in PTCs, was significantly associated with the number of NI/PTC (p = 0.042) and with immunoreactivity for autophagy-associated proteins in the NI (p≤0.035). BRAF-IHC revealed that some of these BRAF-positive thyrocytes contained mutant BRAF in their NI co-localized with autophagy-associated proteins.
conclusionsNI are completely delimited by nuclear membrane in TC. The presence of autophagy-associated proteins within the NI together with degenerated organelles and lysosomal proteases suggests their involvement in autophagy and proteolysis. Whether and how BRAFV600E protein is degraded in NI needs further investigation.
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