New opportunities for preoperative diagnosis of anaplastic thyroid cancer
https://doi.org/10.17650/2222-1468-2021-11-1-34-40
Abstract
Background. Anaplastic thyroid cancer (ATC) is one of the most aggressive human tumors. Since median survival of ATC patients is only 4 months, its early diagnosis is very important. Although ATC has specific clinical manifestations, the analysis of expression of different microRNAs can facilitate preoperative diagnostics and help to detect its potential precursors among differentiated cancers and other thyroid malignancies.
The study objective is to identify microRNAs specific for ATC that are different from microRNAs in other thyroid cancers.
Materials and methods. We analyzed the expression of 14 microRNAs in histological specimens of 67 patients with ATC. The control groups included 25 patients with benign nodules, 36 patients with follicular adenomas, 32 patients with follicular cancer, and 152 patients with papillary thyroid cancer. For 7 out of 67 ATC patients, we compared mi-croRNA levels in histological and cytological specimens.
Results. Patients with ATC demonstrated a statistically significant decrease in the expression of miR-145, miR-125b and increase in the expression of miR-155 and miR-21 compared to all control groups. We found two reliable diagnostic markers of ATC: relative miR-21 expression (at a cutoff of 14.9, sensitivity was 0.955 and specificity was 0.837) and the miR-21/miR-145 ratio (at a cutoff of 122, sensitivity was 0.955 and specificity was 0.955). The level of miR-21 expression and miR-21/miR-145 ratio in cytological specimens were accurate in all 7 cases (100 %).
Conclusion. the level of expression of specific microRNAs can be used as a reliable biomarker for ATC. The consistency between the results obtained in cytological and histological specimens enables the use of stained cytological samples for this analysis.
About the Authors
S. A. LukyanovRussian Federation
Sergey Anatolyevich Lukyanov
64 Vorovsky St., Chelyabinsk 454048
S. V. Sergiyko
Russian Federation
64 Vorovsky St., Chelyabinsk 454048
S. E. Titov
Russian Federation
8/2 Acad. Lavrentiev Ave., Novosibirsk 630090; Bld. 4, 1/1 Arbuzov St., Novosibirsk 630117; 1 Pirogova St., Novosibirsk 630090
Yu. A. Veryaskina
Russian Federation
8/2 Acad. Lavrentiev Ave., Novosibirsk 630090
A. M. Mudunov
Russian Federation
24, Kashirskoe Hwy, Moscow 115522; 3 Tsyurupy St., Moscow 117418
V. Z. Dobrokhotova
Russian Federation
24, Kashirskoe Hwy, Moscow 115522; 3 Tsyurupy St., Moscow 117418
E. S. Kozorezova
Russian Federation
Bld. 2, 8 Oleko Dundicha St., St. Petersburg 192283; 2 Timakova St., Novosibirsk 630060
S. L. Vorobyov
Russian Federation
Bld. 2, 8 Oleko Dundicha St., St. Petersburg 192283
A. V. Vazhenin
Russian Federation
64 Vorovsky St., Chelyabinsk 454048; 42 Blucher St., Chelyabinsk 454087
A. F. Romanchishen
Russian Federation
2 Litovskaya St., St. Petersburg 194100
K. V. Vabalaite
Russian Federation
2 Litovskaya St., St. Petersburg 194100
A. S. Vilkova
Russian Federation
24, Kashirskoe Hwy, Moscow 115522
N. I. Timofeeva
Russian Federation
154 Fontanka River Embankment, St. Petersburg 190103
T. E. Ilinа
Russian Federation
64 Vorovsky St., Chelyabinsk 454048
References
1. Noone A.M., Howlader N., Krapcho M. et al. (eds.). SEER Cancer Statistics Review, 1975-2015. Bethesda, MD. National Cancer Institute. Available from: https://seer.cancer.gov/csr/1975_2015/.
2. Bray F., Ferlay J., Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6):394—424. DOI: 10.3322/caac.21492.
3. Smallridge R.C., Ain K.B., Asa S.L. et al. American Thyroid Association anaplastic thyroid cancer guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2012;22(11):1104—39. DOI: 10.1089/thy.2012.0302.
4. The JAES/JSTS Task Force on the Guidelines for Thyroid Tumors Clinical Practice Guidelines on the Management of Thyroid Tumors 2018. J JAES JSTS 2018;35:1-87.
5. Patel K.N., Shaha A.R. Poorly differentiated and anaplastic thyroid cancer. Cancer Control 2006;13(2):119—28. DOI: 10.1177/107327480601300206.
6. Haymart M.R., Banerjee M., Yin H. et al. Marginal treatment benefit in anaplastic thyroid cancer. Cancer 2013;119(17): 3133—9. DOI: 10.1002/cncr.28187.
7. Lin R.Y. Thyroid cancer stem cells. Nat Rev Endocrinol 2011;7(10):609—16. DOI: 10.1038/nrendo.2011.127.
8. Boerner S., Asa S.L. Biopsy interpretation of the thyroid. Philadelphia: Lippincott Williams & Wilkins, 2009. 276 p.
9. Nikiforova M.N., Tseng G.C., Steward D. et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 2008;93(5):1600—8. DOI: 10.1210/jc.2007-2696.
10. Vargas-Salas S., Martinez J.R., Urra S. et al. Genetic testing for indeterminate thyroid cytology: review and metaanalysis. Endocr Relat Cancer (2018);25(3):R163—77. DOI: 10.1530/ERC-17-0405.
11. Santos M., Buzolin A.L., Gama R.R. et al. Molecular classification of thyroid nodules with indeterminate cytology: development and validation of a highly sensitive and specific new miRNA-based classifier test using fine-needle aspiration smear slides. Thyroid 2018;28(12):1618—26. DOI: 10.1089/thy.2018.0254.
12. Titov S., Demenkov P.S., Lukyanov S.A. et al. Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier. J Clin Pathol 2020;73(11):722—7. DOI: 10.1136/jclinpath-2020-206445.
13. Santiago K., Chen Wongworawat Y., Khan S. Differential microRNA-signa-tures in thyroid cancer subtypes. J Oncol 2020;2020:2052396. DOI: 10.1155/2020/2052396.
14. Geraldo M.V., Kimura E.T. Integrated analysis of thyroid cancer public datasets reveals role of post-transcriptional regulation on tumor progression by targeting of immune system mediators. PLoS One 2015;10(11):e0141726. DOI: 10.1371/journal.pone.0141726.
15. Fassina A., Cappellesso R., Simonato F. et al. A 4-microRNA signature can discriminate primary lymphomas from anaplastic carcinomas in thyroid cytology smears. Cancer Cytopathol 2014;122(4):274—81. DOI: 10.1002/cncy.21383.
Review
For citations:
Lukyanov S.A., Sergiyko S.V., Titov S.E., Veryaskina Yu.A., Mudunov A.M., Dobrokhotova V.Z., Kozorezova E.S., Vorobyov S.L., Vazhenin A.V., Romanchishen A.F., Vabalaite K.V., Vilkova A.S., Timofeeva N.I., Ilinа T.E. New opportunities for preoperative diagnosis of anaplastic thyroid cancer. Head and Neck Tumors (HNT). 2021;11(1):34-40. (In Russ.) https://doi.org/10.17650/2222-1468-2021-11-1-34-40