title: Well-differentiated thyroid cancer with a minor poorly differentiated component: clonal heterogeneity through the prognostic role of CXCR4 and BRAF analysis.
abstract: Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1) <20% PD and (2) 20% to 40% PD, and were studied for CXCR4 expression and BRAF mutation. CXCR4 and molecular testing were distinctly performed on both components of each lesion. The majority of the cases (69%) showed an extrathyroid and metastatic dissemination. Regardless of the 2 categories, we had 8/16 (50%) patients with disease-free status. CXCR4 was negative in all 16 cases, whereas 3 of them (19%) had a mutated BRAF only in the WDC component of the lesion. WDCs with a minor PD pattern, even when <20%, showed more aggressive features than pure WDCs and should be entirely considered as PD carcinoma. The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs.
authors.affiliation: Divisions of *Anatomic Pathology and Histology †Endocrine Surgery ‡Endocrinology, Università Cattolica del Sacro Cuore, "Agostino Gemelli" School of Medicine §Department of Imaging Diagnosis and Biopathology, University of Tor Vergata, Rome, Italy.
authors.forename: Esther D
authors.initials: ED
authors.lastname: Rossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Straccia
authors.forename: Luca
authors.initials: L
authors.lastname: Revelli
authors.forename: Celestino P
authors.initials: CP
authors.lastname: Lombardi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Santeusanio
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002291:Carcinoma, Papillary; D002454:Cell Differentiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf