title: PDCD4 expression in thyroid neoplasia.
abstract: Both the morphogenesis and the molecular pathways of thyroid cancers are controversial. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is controlled by miR-21. By applying immunohistochemistry for PDCD4 and both quantitative real-time PCR (qRT-PCR) and in situ hybridization for miR-21, this study explored PDCD4 expression in human follicular-cell-derived thyroid neoplastic lesions. PDCD4 protein expression was semiquantitatively assessed in 100 consecutive thyroid tumors (25 follicular adenomas (FA), 25 follicular carcinomas (FC), 25 papillary carcinomas (PC), and 25 poorly-differentiated/anaplastic cancers (PD-AC)). Twenty-five additional nonneoplastic thyroid tissue samples were included as controls. To further support the data, miR-21 expression was tested (by qRT-PCR and in situ hybridization) in a different series of 75 cases (15 FAs, 15 FCs, 15 PCs, 15 PD-ACs, and 15 controls). Nonneoplastic thyrocytes consistently featured a strong nuclear PDCD4 expression, while the protein's expression was significantly downregulated in neoplastic epithelia. PDCD4 downregulation was significantly associated with less well-differentiated cancer phenotypes (p < 0.001) and more advanced tumor stages (p < 0.001). Consistently with PDCD4 downregulation, miR-21 was upregulated in neoplastic by comparison with nonneoplastic tissue samples. The present results provide evidence of PDCD4 having a role in thyroid carcinogenesis; further studies should investigate the diagnostic value and the prognostic impact of PDCD4 in thyroid neoplasia.
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Pennelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.forename: Mariangela
authors.initials: M
authors.lastname: Balistreri
authors.forename: Susi
authors.initials: S
authors.lastname: Barollo
authors.forename: Francesca
authors.initials: F
authors.lastname: Galuppini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Pelizzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins