CHARACTERISTICS OF SUBCLONAL STRUCTURE IN THYROCYTE POPULATION IN RADIOIODINE-REFRACTORY METASTASES OF PAPILLARY THYROID CANCER
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.
Markovina, S., Grigsby, P. W., Schwarz, J. K., DeWees, T., Moley, J. F., Siegel, B. A., Perkins, S. M. (2014). Treatment Approach, Surveillance, and Outcome of Well-Differentiated Thyroid Cancer in Childhood and Adolescence. Thyroid, 24 (7), 1121–1126. doi: http://doi.org/10.1089/thy.2013.0297
Haugen, B. R., Alexander, E. K., Bible, K. C., Doherty, G. M., Mandel, S. J., Nikiforov, Y. E. et. al. (2016). 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 26 (1), 1–133. doi: http://doi.org/10.1089/thy.2015.0020
Pacini, F., Ito, Y., Luster, M., Pitoia, F., Robinson, B., Wirth, L. (2012). Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Review of Endocrinology & Metabolism, 7 (5), 541–554. doi: http://doi.org/10.1586/eem.12.36
Pfister, D. G., Fagin, J. A. (2008). Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off. Journal of Clinical Oncology, 26 (29), 4701–4704. doi: http://doi.org/10.1200/jco.2008.17.3682
Deandreis, D., Al Ghuzlan, A., Leboulleux, S., Lacroix, L., Garsi, J. P., Talbot, M. et. al. (2010). Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocrine Related Cancer, 18 (1), 159–169. doi: http://doi.org/10.1677/erc-10-0233
Almendro, V., Marusyk, A., Polyak, K. (2013). Cellular Heterogeneity and Molecular Evolution in Cancer. Annual Review of Pathology: Mechanisms of Disease, 8 (1), 277–302. doi: http://doi.org/10.1146/annurev-pathol-020712-163923
Brychtová, V., Valík, D., Vojtěšek, B. (2018). Variability of Solid Cancer Cell Population and Its Consequences for Cancer Diagnostics and Treatment. Klinicka Onkologie, 31 (2), 2S5–2S13. doi: http://doi.org/10.14735/amko20182s5
Le Pennec, S., Konopka, T., Gacquer, D., Fimereli, D., Tarabichi, M., Tomás, G. et. al. (2015). Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. Endocrine-Related Cancer, 22 (2), 205–216. doi: http://doi.org/10.1530/erc-14-0351
Ling, V., Chambers, A. F., Harris, J. F., Hill, R. P. (1984). Dynamic heterogeneity and metastasis. Journal of Cellular Physiology, 121 (S3), 99–103. doi: http://doi.org/10.1002/jcp.1041210412
Kim, H., Piao, Z., Park, C., Chung, W., Park, C. (1998). Clinical significance of clonality in thyroid nodules. British Journal of Surgery, 85 (8), 1125–1128. doi: http://doi.org/10.1046/j.1365-2168.1998.00783.x
Studer, H., Gerber, H., Zbaeren, J., Peter, H. J. (1992). Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells. Journal of Clinical Endocrinology & Metabolism, 75 (4), 1151–1158. doi: http://doi.org/10.1210/jc.75.4.1151
Mitsutake, N., Iwao, A., Nagai, K., Namba, H., Ohtsuru, A., Saenko, V., Yamashita, S. (2007). Characterization of Side Population in Thyroid Cancer Cell Lines: Cancer Stem-Like Cells Are Enriched Partly But Not Exclusively. Endocrinology, 148 (4), 1797–1803. doi: http://doi.org/10.1210/en.2006-1553
Bozhok, Y.‚ Tavokina, L., Epstein, E. (1996). The new things in diagnostic of thyroid cancer. Optimal combination of morphological and immunocytochemistry research methods of punctious materials. Med Announcer, 138, 40–43.
Zelinskaya, A. (2019). Citokeratin 17 i tireoidna peroksidaza v yakosti imunocitohimichnih markeriv dooperaciynogo prognozuvannya radioiodrezistentnosti ta efektivnosti radioiodterapii papilyarnogo raku shitopodibnoi zalozi. Onkologiya, 21 (1), 31–35.
Latza, U., Niedobitek, G., Schwarting, R., Nekarda, H., Stein, H. (1990). Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. Journal of Clinical Pathology, 43 (3), 213–219. doi: http://doi.org/10.1136/jcp.43.3.213
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