Abstract
The aim of the study was cytological and immunocytochemical researches of thyrocyte populations in fine-needle aspiration smears of radioiodine-refractory metastases and their comparison with radioiodine-avid metastases and corresponding primary papillary carcinoma of the thyroid. Materials and Methods. The cytomorphological and immunocytochemical researches were conducted on the fine needle aspiration smears of 60 papillary thyroid carcinomas and 104 metastases, which were detected in the postoperative period. We applied the indirect immunoperoxidase technique using primary monoclonal mouse antibodies against leukocyte-common antigen, macrophage antigen, thyroglobulin, epithelial cell adhesion molecule, cytokeratines 7.8, polyclonal rabbit antibodies against calcitonin. Results. It was demonstrated, that radioiodine-avid metastases and corresponding primary papillary thyroid carcinoma smears had first type of cellular population with a relatively regular location of thyrocytes. Unlike them, radioiodine-refractory metastases smears had the second type of cellular population with irregularly location of thyrocytes among which showed up two cellular phenotypes. In our investigated smears some special cellular complexes were found – in 21 % of radioiodine-refractory metastases, 1 % in radioiodine-avid metastases and none of it in corresponding primary papillary thyroid. The cytological sign of cystic degeneration was found in 58 % of radioiodine-refractory metastases, but in radioiodine-avid metastases – was absent. Conclusion. The radioiodine-refractory metastases of papillary thyroid cancer demonstrated their distinction from radioiodine-uptake metastases with a presence of phenotypic heterogeneity. It is shown, that an appearance of certain cell subpopulations, special cellular complexes and cystic degeneration in fine-needle aspiration smears of radioiodine-refractory metastases, which in radioiodine-uptake metastases and corresponding primary papillary thyroid carcinomas were not found, can be used during the preoperative period to forecast the impossibility of radioiodine treatment.
Highlights
Applying of radioiodine therapy, which is based on the ability of follicular epithelium to accumulate radioiodine (RI), underlies the advantageous prognosis of differentiated thyroid cancer (DTC) [1, 2]
The comparative cytological and immunocytochemical research of thyrocyte populations on smears of radioiodine-refractory metastases (RIRM), RIAM and corresponding primary PTC (PPTC) demonstrated the phenotypic heterogeneity in RIRM epithelium and its absence in the rest of the groups
RIAM and corresponding PPTC smears had the first type of cellular population, which comprised small epithelial cells (12–20 microns) with moderate nuclear-cytoplasmic ratios that had amphophilic or faintly oxyphilic cytoplasm
Summary
Applying of radioiodine therapy, which is based on the ability of follicular epithelium to accumulate radioiodine (RI), underlies the advantageous prognosis of differentiated thyroid cancer (DTC) [1, 2]. The data regarding a tumors’ resistance to a commonly used therapy has shown that the clonal tumor heterogeneity may be based on its development [6, 7] Both theories of oncogenesis (stochastic theory of clonal evolution and cancer stem cell hypothesis) indicate that the monoclonal population of malignant tumor cells breaks down into a number of subclones and becomes phenotypically heterogeneous because of genetic and epigenetic changes [8, 9]. This may have a clinical implication for the disease’s progress and tumor therapy [10]. The detection of cellular phenotypes that are associated with radioiodine refractoriness is of current interest to examination of the thyrocyte population in radioiodine-refractory metastases (RIRM) of papil-
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