ID Proteins May Reduce Aggressiveness of Thyroid Tumors
ID genes have an important function in the cell cycle, and ID proteins may help identify aggressive tumors, besides being considered promising therapeutic targets. However, their role in thyroid tumors is still poorly understood. We examined ID expression and their correlation with diagnostic and prognostic features aiming to find a clinical application in differentiated thyroid carcinoma (DTC) cases. mRNA levels of ID1, ID2, ID3, and ID4 genes were quantified and their expression was observed by immunohistochemistry in 194 thyroid samples including 68 goiters, 16 follicular adenomas, 75 classic papillary thyroid carcinomas, 18 follicular variants of papillary thyroid carcinoma, 5 follicular thyroid carcinomas, and 1 anaplastic thyroid cancer, besides 11 normal thyroid tissues. DTC patients were managed according to standard protocols and followed up for M = 28 ± 16 months. ID2, ID3, and ID4 mRNA levels were higher in benign (2.0 ± 1.9; 0.6 ± 0.6; and 0.7 ± 1.0 AU, respectively) than those in malignant nodules (0.30 ± 0.62; 0.3 ± 0.3; and 0.2 ± 0.3 AU, respectively, p < 0.0001 for all three genes) and were associated with no extra thyroid invasion or metastasis at diagnosis. ID3 nuclear protein expression was higher in benign than that in malignant cells (5.2 ± 0.9 vs 3.0 ± 1.8 AU; p < 0.0001). On the contrary, the cytoplasmic expression of ID3 was higher in malignant than that in benign lesions (5.7 ± 1.5 vs 4.0 ± 1.4 AU; p < 0.0001). Our data indicate that ID genes are involved in thyroid tumorigenesis and suggest these genes act impeding the evolution of more aggressive phenotypes. The different patterns of their tissue expression may help identify malignancy and characterize thyroid lesion aggressiveness.
KeywordsID genes bHLH Thyroid cancer Aggressiveness
The authors thank Paulo Latuf Filho and Caroline Bondarik for the services provided in the immunohistochemistry reaction. A special thanks to Joseane Morari and Simoni Avansini for their help in the RNA FFPE extraction and real-time PCR technique, to Amanda Karina Loyolla for the adjustments on the figures, and to our group from the Laboratory of Cancer Molecular Genetics (GEMOCA) of the School of Medical Sciences. The authors also thank Espaço da Escrita – Pró-Reitoria de Pesquisa - UNICAMP - for the language services provided.
Laís Helena Pereira Amaral performed and designed the research, analyzed the data, and wrote the paper. Natássia Elena Bufalo contributed with the research design and development. Karina Colombera Peres contributed with data of the samples and analysis. Icleia Siqueira Barreto performed immunohistochemistry and data analysis. Antonio Hugo José Marques Fróes contributed with all the samples and their data. Laura Sterian Ward idealized and designed the study, analyzed data, and reviewed the paper.
Compliance with Ethical Standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study, formal consent is not required.
Conflict of Interest
The authors declare that they have no conflict of interest.
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