Chromogenic in Situ-Hybridization of HPV16/18 DNA in Relation to the Over-Expressed Protein of P73-Gene in Tissues from a Group of Thyroid Carcinoma

Document Type : Original Articles

Authors

1 Ministry of Health, Baghdad, Iraq

2 Clinical Communicable Diseases Research, College of Medicine, University of Baghdad, Baghdad, Iraq

3 Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq

Abstract

Thyroid cancer has been related to many environmental, genetic, and viral factors. Human Papilloma Viruses (HPV) are epitheliotropic viruses infecting cutaneous and mucosal tissues, leading to a variety of benign and malignant tumors. The p73-gene expresses two important isoforms from the N-terminal end with two opposite activities in the regulation of cell fate. The present study aimed to assess the histopathological expression of tissues from thyroid cancers in relation to the over-expression of the p73 gene with HPV 16/18 infection. A total of 116 thyroid tissues were examined for HPV 16/18-DNA and P73-gene protein expression. The samples belonged to 36 patients diagnosed with thyroid carcinoma, 40 thyroid adenoma tissues blocks, and 40 apparently normal thyroid tissues. The detection of HPV 16/18-DNA was performed by in situ hybridization (ISH), whereas P73 gene expression was carried out by immunohistochemistry (IHC). The HPV16/18 DNA-ISH reactions in thyroid cancers were found in 72.2% tissues, 35% HPV16/18- positivity was detected in the thyroid adenoma tissues group, and 27.5% of healthy thyroid tissues revealed ISH reactions. Statistically, the difference of the HPV16/18 in thyroid cancers and control was highly significant. The p73 was detected in 66.7% and 57.5% of thyroid cancer and adenoma thyroid tissues, respectively, while 45% of the examined healthy thyroid tissues revealed IHC-reactions. The difference between the p73-protein expression percentages detected in tissues of thyroid tumors and the control group was non statistically significant. The presence of HPV16/18, as well as an over-expressed p73-gene, in thyroid cancer patients, suggests that the virus, as well as this protein, may play an etiologic role in thyroid carcinogenesis.

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Main Subjects


  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
  2. HealthEnvironment Mo. Annual Report Iraqi Cancer Registry 2016. Iraqi Cancer Board. 2018:23.
  3. WHO. cancer fact sheet, february 2018.”. 2018.
  4. Ahn HS, Kim HJ, Kim KH, Lee YS, Han SJ, Kim Y, et al. Thyroid cancer screening in South Korea increases detection of papillary cancers with no impact on other subtypes or thyroid cancer mortality. Thyroid. 2016;26(11):1535-40.
  5. Ospina NS, Iñiguez-Ariza NM, Castro MR. Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment. BMJ. 2020;368.
  6. Smallridge R, Copland J. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol. 2010;22(6):486-97.
  7. Mohammed SH, Abed-AlkadumAlajeely A, Ameer AAHA, Ali SHM, Abed_Azuwaid AA. Molecular localization of human papillomaviru-18 (HPV-18) in tissues from thyroid carcinoma in Mid-Euphrate-Iraq. Adv Nat Appl Sci.. 2015;9(14):25-32.
  8. Mostafaei S, Keshavarz M, Nahand JS, Hassankiadeh RF, Moradinazar M, Nouri M, et al. Viral infections and risk of thyroid Cancer: a systematic review and empirical Bayesian meta-analysis. Pathol Res Pract. 2020;216(4):152855.
  9. Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal Maso L. Worldwide thyroid-cancer epidemic? The increasing impact of overdiagnosis. N Engl J Med. 2016;375(7):614-7.
  10. Riedel S, Morse SA, Mietzner TA, Miller S. Jawetz Melnick & Adelbergs Medical Microbiology 28 E: McGraw Hill Professional; 2019.
  11. Spinner C, Ding L, Bernstein DI, Brown DR, Franco EL, Covert C, et al. Human papillomavirus vaccine effectiveness and herd protection in young women. Pediatrics. 2019;143(2).
  12. Ballini A, Dipalma G, Isacco CG, Boccellino M, Di Domenico M, Santacroce L, et al. Oral microbiota and immune system crosstalk: A translational research. Biology. 2020;9(6):131.
  13. Burley M, Roberts S, Parish JL, editors. Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Seminars in Immunopathology; 2020: Springer.
  14. Santacroce L, Di Cosola MD, Bottalico L, Topi S, Charitos IA, Ballini A, et al. Focus on HPV infection and the molecular mechanisms of oral carcinogenesis. Viruses. 2021;13(4):559.
  15. Oyervides-Muñoz MA, Pérez-Maya AA, Rodríguez-Gutiérrez HF, Gómez-Macias GS, Fajardo-Ramírez OR, Treviño V, et al. Understanding the HPV integration and its progression to cervical cancer. Infect Genet Evol. 2018;61:134-44.
  16. Yeo-Teh NS, Ito Y, Jha S. High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. Int J Mol Sci. 2018;19(6):1706.
  17. Wang-Shick R. Molecular virology of human pathogenic viruses. Elsevier Inc. Academic Press; 2017.
  18. Martini FH, Nath JL, Bartholomew EF, Ober W. Fundamentals of Anatomy and Physiology. 2001. Pentice Hall: New Jersey. 2015:538-57.
  19. Patel NS, Sheykholeslami K. Papillary carcinoma in thyroglossal duct cyst: Two case reports and review of the literature. Ear Nose Throat J. 2016;95(3).
  20. Hall JE. Guyton y hall: Elsevier Health Sciences Spain; 2011.
  21. Vincenzo De Sanctis M, Soliman AT, Di S, Maio M, Elsedfy H, Soliman NA, et al. Thyroid hemiagenesis from childhood to adulthood: review of literature and personal experience. Pediatr Endocrinol Rev. 2016;13(3).
  22. Omran Z, H Dalhat M, Abdullah O, Kaleem M, Hosawi S, A Al-Abbasi F, et al. Targeting Post-Translational Modifications of the p73 Protein: A Promising Therapeutic Strategy for Tumors. Cancers. 2021;13(8):1916.
  23. Uboveja A, Satija YK, Siraj F, Sharma I, Saluja D. p73–NAV3 axis plays a critical role in suppression of colon cancer metastasis. Oncogenesis. 2020;9(2):1-15.
  24. Al-Alwany SHM, Al_Saffar AKH, Kadhum SA, Ali SHM, Ali JA. Molecular Detection of Cytomegalo, CDK2 and P27 in Tissues from Patients with Thyroid Carcinoma. 2009.
  25. Hussain AM, Lafta RK. Cancer Trends in Iraq 2000–2016. Oman Med J. 2021;36(1):219.
  26. Moini J, Pereira K, Samsam M. Epidemiology of Thyroid Disorders: Elsevier; 2020.
  27. Moghoofei M, Mostafaei S, Nesaei A, Etemadi A, Sadri Nahand J, Mirzaei H, et al. Epstein–Barr virus and thyroid cancer: The role of viral expressed proteins. J Cell Physiol. 2019;234(4):3790-9.
  28. Mohammed SH, Alajeely AA-A, Ameer AAHA, Ali SHM, Azuwaid AAA. Molecular Localization of Human Papillomaviru_18 (HPV_18) in Tissues from Thyroid Carcinoma in Mid-Euphrates. J Univ Babylon Pure Appl Sci. 2018;26(6):84-94.
  29. Dialameh PA, Saki F, Monabbati A, Dehghanian A, Valibeigi B, Soveid M. Detection of human papillomavirus in papillary thyroid carcinoma and its association with tumor staging and pathologic features. Iran J Med Sci. 2021;46(4):256.
  30. Syrjänen S. Oral manifestations of human papillomavirus infections. Eur J Oral Sci. 2018;126:49-66.
  31. Bansal A, Singh MP, Rai B. Human papillomavirus-associated cancers: A growing global problem. Int J Appl Basic Med. 2016;6(2):84.
  32. Kamal M, Lameiras S, Deloger M, Morel A, Vacher S, Lecerf C, et al. Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site. Br J Cancer. 2021;124(4):777-85.
  1. Nkili-Meyong AA, Moussavou-Boundzanga P, Labouba I, Koumakpayi IH, Jeannot E, Descorps-Declère S, et al. Genome-wide profiling of human papillomavirus DNA integration in liquid-based cytology specimens from a Gabonese female population using HPV capture technology. Sci Rep. 2019;9(1):1-11.
  2. Logotheti S, Richter C, Murr N, Spitschak A, Marquardt S, Pützer BM. Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond. Front Cell Dev Biol. 2021:2733.
  3. Ramos H, Raimundo L, Saraiva L. p73: From the p53 shadow to a major pharmacological target in anticancer therapy. Pharmacol Res. 2020;162:105245.
  4. Yoon M-K, Ha J-H, Lee M-S, Chi S-W. Structure and apoptotic function of p73. BMB Rep. 2015;48(2):81.
  5. Rufini A, Agostini M, Grespi F, Tomasini R, Sayan BS, Niklison-Chirou MV, et al. p73 in Cancer. Gene Cancer. 2011;2(4):491-502.
  6. Manzella L, Stella S, Pennisi MS, Tirrò E, Massimino M, Romano C, et al. New insights in thyroid cancer and p53 family proteins. Int J Mol Sciz. 2017;18(6):1325.
  7. Martinez-Zapien D, Ruiz FX, Poirson J, Mitschler A, Ramirez J, Forster A, et al. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature. 2016;529(7587):541-5.