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.