Online ISSN: 3007-0244,
Print ISSN:  2410-4280
IMMUNOHISTOCHEMICAL ANALYSIS EXPRESSION TP73 IN ONCOCYTIC FOLLICULAR ADENOMA OF THE THYROID

Oncocytic follicular adenomas (FAs) of the thyroid are cells neoplasms of follicular origin that predominantly consist of large polygonal cells with eosinophilic and granular cytoplasm. According to some scientific studies, TP73 might play a сertain role in tumor genesis (oncogenesis). Moreover, due to the absence of p53, oncogenes may attract p73 to induce apoptosis in tumor cells. TP53 is a crucial tumor suppressor in preventing the cancerous transformation of cells. There was also a particular focus on the amplification of 1p36 chromosome in oncocytic FA, which contains a tumor nidus of TP73 protein, which is a member of the p53 family, involved as a factor of the cancerous tumor development.

The aim: To evaluate the extent of the genomic instability in oncocytic follicular adenoma of the thyroid.

Materials and Methods: Twenty-four surgically resected formalin-fixed, paraffin-embedded (FFPE) thyroid tumors, including 12 oncocytic and 12 normal FAs, were available for the current study. As it was a retrospective research with minimal risk to the participants, informing patients and taking their consent was not necessary. The study was authorized by the ethics committee of the Biomedical Sciences High School of Nagasaki University (protocol No. 15062617) and permitted by the ethics committee of the State Medical University, Semey (Protocol No. 5, December 15, 2015). The study of archival data of patients with follicular adenoma of the thyroid was conducted between 2014 and 2016 in the department of pathomorphology and cytochemistry of the "Regional Oncology Center" (Semey city, Kazakhstan) and in the scientific laboratory of the Nagasaki University (Japan).

For processing of the research results were used the Mann-Whitney-U test, the exact Fisher measure, Pearson's correlation analysis. The calculation was made with a help of SAS software (version 8:2, SAS Institute, Cary, NC, USA). All tests were unilateral and р < 0,05 was considered to be statistically true measure.

Results: Patients with oncocytic follicular adenoma were older than with normal follicular adenoma (p = 0.03) and there was no statistically significant difference in tumor size. The study showed, that the frequency of unstable expression of 53BP1 was vastly higher in the oncocytic follicular adenoma than in the usual one (p = 0.0028). Our work demonstrated that the level of TP73 immunoreactivity was greatly higher in oncocytic than in normal FA (p= 0,0001). We have found a significant positive correlation (r = 0.5983, p = 0.0020) between the percentage of tumour cells expressing unstable type of 53BP1 and the percentage of cells being positive for TP73 expression in oncocytic FA.

Conclusion: It is important to note that we have found a significant positive correlation between the percentage of tumour cells expressing unstable type of 53BP1 and the percentage of cells being positive for TP73 expression in oncocytic follicular adenoma. All these data indicate that the oncocytic follicular adenoma demonstrates an elevated level of TP73 protein, which correlates with the appearance of a DNA double strand break.

Zhanna U. Kozykenova, http://orcid.org/0000-0001-7420-2279

Semey State Medical University, Semey, Kazakhstan

1. Bourdon J.C. 2007. p53 and its isoforms in cancer. Br. J. Cancer 97: 277–282.

2. Bourdon J.C., Fernandes K., Murray-Zmijewski F., Liu G., Diot A., Xirodimas D.P., Saville M.K., Lane D.P. p53 isoforms can regulate p53 transcriptional activity.Genes & Dev. 2005. 19: 2122–2137.

3. Bullock A.N., Fersht A.R. Rescuing the function of mutant p53. Nat. Rev. Cancer., 2001. 1, 68–76.

4. Castillo J., Goni S., Latasa M.U., Perugorria M.J., Calvo A. et al. Amphiregulin induces the alternative splicing of p73 into its oncogenic isoform DeltaEx2p73 in human hepatocellular tumors. Gastroenterology. 2009. 137:1805-1815.

5. Carcangiu M.L., Bianchi S., Savino D., Voynick I.M., Rosai J. Follicular Hurthle cell tumors of the thyroid gland. Cancer. 1991. 68: 1944-1953.

6. Canberk S., Griffin A.C., Goyal A., Wang H., Montone K. et al. Oncocytic follicular nodules of the thyroid with or without chronic lymphocytic thyroiditis: An institutional experience. Cytojournal. 2013. 10: 2.

7. Chao T.C., Lin J.D., Chen M.F. Surgical treatment of Hurthle cell tumors of the thyroid. World J Surg. 2005. 29:164-168.

8. DeYoung M.P., Ellisen L.W. p63 and p73 in human cancer: Defining the network. Oncogene 2007. 26: 5169–5183.

9. Di Como C.J., Gaiddon C., Prives C. p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol. Cell. Biol. 1999. 19: 1438–1449.

10. Frisk T., Kytola S., Wallin G. Low frequency of numerical chromosomal aberrations in follicular thyroid tumors detected by comparative genomic hybridization. Genes Chromosomes Cancer 1999. 25: 349-353.

11. Ghossein R.A., Hiltzik D.H., Carlson D.L., Patel S., Shaha A. et al. Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases. Cancer. 2006. 106: 1669-1676.

12. Haq M., Harmer C. Differentiated thyroid carcinoma with distant metastases at presentation: prognostic factors and outcome. Clin Endocrinol (Oxf). 2005. 63:87-93.

13. Hemmer S., Wasenius V.M., Knuutila S., Joensuu H., Franssila K. Comparison of benign and malignant follicular thyroid tumours by comparative genomic hybridization. Br J Cancer 1998. 78: 1012-1017.

14. Levrero M., De Laurenzi V., Costanzo A., Gong J., Wang J.Y., Melino G. The p53/p63/p73 family of transcription factors:overlapping and distinct functions. J. Cell Sci., 2000. 113, 1661–1670.

15. Maximo V., Lima J., Prazeres H., Soares P., Sobrinho-Simoes M. The biology and the genetics of Hurthle cell tumors of the thyroid. Endocr Relat Cancer. 2012. 19: R131-147.

16. McDonald M.P., Sanders L.E., Silverman M.L., Chan H.S., Buyske J. Hurthle cell carcinoma of the thyroid gland: prognostic factors and results of surgical treatment. Surgery. 1996. 120: 1000-1004.

17. Montone K.T., Baloch Z.W., LiVolsi V.A. The thyroid Hurthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008. 132: 1241-1250.

18. Moll U.M. Slade N. p63 and p73: Roles in development and tumor formation. Mol. Cancer Res. 2004. 2: 371–386.

19. Murray-Zmijewski F., Lane D.P., Bourdon J.C. p53/p63/p73 isoforms: An orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006. 13: 962–972.

20. Nakashima M., Suzuki K. et al. Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis. Int J Cancer. 2008. 122: 1082-1088.

21. Petric R., Gazic B., Besic N. Prognostic factors for disease-specific survival in 108 patients with Hurthle cell thyroid carcinoma: a single-institution experience. BMC Cancer. 2014. 14: 777.

22. Rosai J., Kuhn E., Carcangiu M.L. Pitfalls in thyroid tumour pathology. Histopathology. 2006. 49: 107-120.

23. Rosai J. Thyroid gland. In: Rosai J (ed) Rosai and Ackerman’s Surgical Pathology (9th). Mosby, New York: 2004. 544-547.

24. Shaha A.R., Loree T.R., Shah J.P. Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery. 1995. 118: 1131-1136.

25. Sugino K., Ito K., Mimura T., Kameyama K., Iwasaki H. et al. Hurthle cell tumor of the thyroid: analysis of 188 cases. World J Surg 2001. 25: 1160-1163.

26.Tallini G., Hsueh A., Liu S., Garcia-Rostan G. et al. Frequent chromosomal DNA unbalance in thyroid oncocytic (Hurthle cell) neoplasms detected by comparative genomic hybridization. Lab Invest. 1999. 79: 547-555.].

27. Vilgelm A.E., Washington M.K., Wei J., Chen H., Prassolov V.S. et al. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors. Mol Cancer Ther. 2010.  9: 693-705.

28. Wada N., Duh Q.Y., Miura D., Brunaud L., Wong M.G. et al. Chromosomal aberrations by comparative genomic hybridization in hurthle cell thyroid carcinomas are associated with tumor recurrence. J Clin Endocrinol Metab. 2002. 87: 4595-4601.

29. Wei S., LiVolsi V.A., Montone K.T., Morrissette J.J., Baloch Z.W. PTEN and TP53 Mutations in Oncocytic Follicular Carcinoma. Endocr Patho.l 2015. 26: 365-369.

30. Yang A., Kaghad M., Caput D. McKeon F. On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet, 2002. 18, 90–95.

31. Yang A., Kaghad M., Wang Y., Gillett E., Fleming M.D. et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998. 2: 305-316.

Number of Views: 846


Category of articles: Original article

Bibliography link

Kozykenova Zh.U. Immunohistochemical analysis expression TP73 in oncocytic follicular adenoma of the thyroid. Nauka i Zdravookhranenie [Science & Healthcare]. 2017, 1, pp. 64-73.

Авторизируйтесь для отправки комментариев