title: Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant.
abstract: The cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. Several studies have identified alterations in the expression profiles of those molecules in different histotypes of thyroid carcinoma. The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare, highly invasive variant of PTC in which an impairment of cell-cell adhesion may play a major role. In an attempt to progress in the understanding of the clinicopathological features of DSV, this study examined eight cases of DSV, 18 cases of classical PTC and a control group of normal thyroid by immunohistochemistry (E-, P- and N-cadherins and beta-, gamma- and alpha-catenins). The E-cadherin gene was also studied by polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) and methylation-specific PCR (MSP). In contrast to classical PTC, which showed heterogeneous loss of E-cadherin expression, in almost every case of DSV a pronounced reduction was observed in its membranous expression, accompanied by a relocation to the cytoplasm. Inactivation of the E-cadherin/catenin complex appears to occur in DSV via two different pathways: E-cadherin alteration either through mutation (one out of the eight cases) or through methylation of the E-cadherin gene promoter (three out of five cases); and beta- and/or gamma-catenin alterations (three of the eight cases). Methylation of the E-cadherin gene promoter, abnormalities of E-cadherin expression and alterations of gamma-catenin were also detected in classical PTC. In DSV, as in classical PTC, there is neo-expression of P-cadherin in areas of squamous metaplasia and no N-cadherin expression. In conclusion, abnormalities of the E-cadherin/catenin complex appear to be more pronounced in DSV than in classical PTC. It remains to be shown whether or not such differences are associated with the more aggressive behaviour of DSV compared with classical PTC.
authors: IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto) Porto, Portugal.
authors: A S
authors: AS
authors: Rocha
authors: P
authors: P
authors: Soares
authors: R
authors: R
authors: Seruca
authors: V
authors: V
authors: Máximo
authors: X
authors: X
authors: Matias-Guiu
authors: J
authors: J
authors: Cameselle-Teijeiro
authors: M
authors: M
authors: Sobrinho-Simões
mesh_terms: D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics; D019175:DNA Methylation; D051180:Desmoplakins; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D013961:Thyroid Gland / Q000737:chemistry; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000473:pathology; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin