PDCD4 expression in thyroid neoplasia
Gianmaria Pennelli1, Matteo Fassan, Caterina Mian
1Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
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.
Insights
Programmed cell death 4 (PDCD4) is downregulated in thyroid tumors, while miR-21 is upregulated. This suggests PDCD4 plays a role in thyroid cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thyroid cancer development involves complex morphogenesis and molecular pathways.
- Programmed cell death 4 (PDCD4) is a known tumor suppressor gene.
- PDCD4 expression is regulated by microRNA-21 (miR-21).
Purpose of the Study:
- To investigate the expression of PDCD4 in human follicular-cell-derived thyroid neoplastic lesions.
- To explore the relationship between PDCD4 expression and miR-21 levels in thyroid tumors.
- To assess the association of PDCD4 downregulation with clinicopathological features of thyroid cancer.
Main Methods:
- Immunohistochemistry was used to assess PDCD4 protein expression in 100 thyroid tumors and 25 controls.
- Quantitative real-time PCR (qRT-PCR) and in situ hybridization were employed to measure miR-21 expression in 75 cases.
- Thyroid tumors included follicular adenomas, follicular carcinomas, papillary carcinomas, and poorly-differentiated/anaplastic cancers.
Main Results:
- Nonneoplastic thyroid cells exhibited strong nuclear PDCD4 expression.
- PDCD4 protein expression was significantly downregulated in all types of thyroid neoplastic lesions compared to controls.
- PDCD4 downregulation correlated significantly with less differentiated cancer phenotypes and advanced tumor stages.
- miR-21 expression was consistently upregulated in neoplastic thyroid tissues relative to nonneoplastic tissues.
Conclusions:
- PDCD4 exhibits a significant role in thyroid carcinogenesis.
- Downregulation of PDCD4 and upregulation of miR-21 are associated with thyroid neoplasia.
- Further research is warranted to evaluate the diagnostic and prognostic potential of PDCD4 in thyroid cancer.
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