| Autor: |
Ignjatović Jocić V; Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia., Janković Miljuš J; Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia., Išić Denčić T; Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia., Živaljević V; Center for Endocrine Surgery, University Clinical Center of Serbia, Doktora Subotića 13, 11000 Belgrade, Serbia., Tatić S; Institute for Pathology, Faculty of Medicine, University of Belgrade, Doktora Subotića Starijeg 1, 11000 Belgrade, Serbia., Đorić I; Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia., Šelemetjev S; Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia. |
| Abstrakt: |
Thyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 and on a posttranslational level by autophosphorylation at Y397 (pY397-FAK). We related regulators of FAK with histologic dedifferentiation, clinicopathological factors, and differential diagnosis in the thyroid neoplasia spectrum. We classified 82 cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variants of papillary thyroid carcinoma (PTC), dedifferentiated PTC, and anaplastic carcinoma. MiRs were analyzed by RT-qPCR. Protein expression of pY397-FAK was analyzed by immunohistochemistry (separately in the membrane, cytoplasm, and nuclear compartment) and Western blot. All three miRs were upregulated in healthy tissue compared to malignant, while pY397-FAK was downregulated. MiRs and pY397-FAK were not mutually correlated. MiR-135a-5p was decreasing while membranous and cytoplasmic pY397-FAK increased with dedifferentiation. Neither miR correlated with clinicopathological factors. MiR-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK discriminated the follicular from the classical variant of PTC. Disturbances of FAK regulation on different levels contribute to neoplastic dedifferentiation. pY397-FAK exerts its oncogenic role in the membrane and cytoplasm. Diagnostically, miRs-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK differentiated between classical and follicular PTC. |
