Zelinska G. Cytological aspects of radioiodine resistance of papillary thyroid cancer metastases and algorithm of their preoperative prediction

Object of the research: radioiodistance of papillary thyroid cancer (PTC). Aim: The goal of the dissertation was determinate the role of the violation expression and activity of certain antigens in evolving of radioiodine resistance and development of the methods pre-operative prediction of the radioiodine resistance and efficiency of the radioiodine therapy on the material of Fine Needle Aspiration (FNA) smears. Methods of the investigation and equipment: cytological, immunocytochemical, cytochemical, mathematical, statistical; light microscope Olympus CX41, LEICA DMLS. Theoretical and practical results: The theoretical significance of the dissertation is that the obtained scientific results allowed to get an idea of cytological, immunocytochemical, and cytochemical changes that occur during the development of radioiodine resistance to PTC, which allowed to develop a new approach to preoperative prediction of radioiodine resistance and radioiodine therapy. Identification of the antigenic profile of cells of radioiodine-resistant metastases (RIRM) allowed for the first time to develop methods of preoperative prediction of radioiodine resistance and effectiveness of radioiodine therapy of PTC, which are implemented in specialized facilities. The developed methods are fast, easy to use and allow to determine personalized tactics of monitoring and treatment of patients with PTC - to deprive patients with RIRM of unnecessary courses of radioiodine therapy, and for patients with metastases that accumulate radioiodine, to use radioiodine therapy instead of surgery. Novelty: Cytological and immunocytochemical study of the subclonal structure of the thyrocyte population punctates of PTC metastases detected in the postoperative period was conducted for the first time. The presence of phenotypic heterogeneity of thyrocytes of RIRMs of PTC was demonstrated in contrast to the absence of such feature for radioiodine–avid metastases (RIAM). It is proved that certain cellular subpopulations which differ from other thyrocytes by immunocytochemical and cytological characteristics. It was found that the frequency of regional metastases of PTC correlates with the presence of a special cellular subpopulation in FNA smears of primary PTC. For the first time there was a study of the correlation of the frequency of micronucleis in the FNA smears of PTC’ metastases depending on their ability to accumulate radioiodine. No statistically significant difference was found between the content of micronucleis in the epithelium of punctates’ RIRM and RIAM of PTC. The result of the work showed that the radioiodine resistance of PTC metastases correlates with the presence of cytological signs of cystic degeneration in the FNA smears of postoperative metastases. The correlation between the thyrocytes’ content with thyroid peroxidase in the FNA smears of primary PTC and the presence of metastases in the studied patients in the postoperative period is shown. Immunocytochemical studies of the FNA smears of metastases that developed after thyroidectomy and radioiodine therapy revealed a significant difference in the percentage of thyrocytes containing thyroid peroxidase and thyroglobulin between RIRM and RIAM. It is shown that the effectiveness of radioiodine therapy depends on the expression of thyroid peroxidase in the sites of PTC metastases. Comparison of cytochemical and immunocytochemical methods for determining the expression of thyroid peroxidase in the epithelium of FNA smears of postoperative RIRM and RIAM demonstrated comparable results of both methods of research, which substantiates the possibility of using both methods in the preoperative prediction of radioiodine resistance of PTC. It has been determined that the phenomenon of radioiodine resistance does not correlate with a decrease or increase in the proliferative activity of epithelium of metastases of PCT. The cytological and immunocytochemical changes in the dynamics of development of secondary radioiodine resistance and of repeated metastasis of PTC were first investigated. As a result of complex studies of FNA smears of PTC and their metastases, for the first time an algorithm for preoperative prediction of radioiodine resistance and efficacy of radioiodine therapy of PTC, which can be used in the practice of radiology, endocrinology, oncology clinics’ departments. The degree of implementation: the results of research are used in the work of the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of Natіonal Academy of Medical Sciences of Ukraine», State Institution «V.Ya. Danilevsky Institute of Endocrine Pathology of National Academy of Medical Sciences of Ukraine», National Cancer Institute. Areas of application: endocrinology.