{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:34:24Z","timestamp":1764653664518,"version":"3.46.0"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007514","name":"University of Pisa","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The 2022 WHO classification gives more importance to the integration of morphological and molecular characteristics of tumors, introducing new diagnostic criteria for papillary thyroid carcinoma (PTC). The invasive encapsulated follicular variant of PTC (IEFVPTC) is now considered a separate entity and no longer a subtype of PTC, while the infiltrative follicular variant (IFVPTC) is still considered a PTC subtype. The separation of invasive encapsulated follicular variants from PTCs implies that differential diagnosis between IEFVPTC and IFVPTC can be difficult. We performed a gene expression analysis by NanoString technology on 23 PTCs, divided into 11 IEFVPTCs and 12 IFVPTCs. We focused our attention on the possible role of the tumor microenvironment (TME) and, in particular, the role of the extracellular matrix (ECM). IFVPTC, compared to IEFVPTC, showed a statistically significant downregulation of 2 genes and an upregulation of 45. Among these genes, we focused our attention on TIMP2 and COL1A2, whose high upregulation was statistically significant in IFVPTC. TIMP2 and COL1A2 are involved in ECM degradation and synthesis and in collagen biosynthesis and modification. The ECM and collagen alterations in IFVPTC could reflect the different tumor behavior of FVPTCs, allowing the identification of new biomarkers to distinguish IEFVPTC from IFVPTC.<\/jats:p>","DOI":"10.3390\/biom15121666","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Differences in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (IEFVPTC) and Infiltrative Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC): The Role of Extracellular Matrix"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9178-2120","authenticated-orcid":false,"given":"Rebecca","family":"Sparavelli","sequence":"first","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-0219","authenticated-orcid":false,"given":"Riccardo","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5904-3708","authenticated-orcid":false,"given":"Laura","family":"Boldrini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Fuochi","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnese","family":"Proietti","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3769-8783","authenticated-orcid":false,"given":"Francesca","family":"Signorini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liborio","family":"Torregrossa","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-516X","authenticated-orcid":false,"given":"Gabriele","family":"Materazzi","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Ugolini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s12020-023-03336-4","article-title":"The 5th edition of WHO classification of tumors of endocrine organs: Changes in the diagnosis of follicular-derived thyroid carcinoma","volume":"80","author":"Basolo","year":"2023","journal-title":"Endocrine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3803\/EnM.2022.1553","article-title":"Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach","volume":"37","author":"Jung","year":"2022","journal-title":"Endocrinol. 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