Document Type : Original Research


Department of Pathology, Faculty of Medicine, Fayoum University, Egypt


Background & Objective: One of the most prevalent endocrine system cancers is papillary thyroid carcinoma, with complicated predisposing factors and pathogenesis. YAP1 (Yes-associated protein 1) is a well-known oncogene; its activity is increased in a variety of human malignancies and has recently been paid great attention. The present study examines YAP1 and P53 immunohistochemical expression in papillary thyroid carcinoma and investigates the association of their expression with the available clinicopathological risk factors to assess their possible prognostic role.
Methods: The current study used paraffin blocks of 60 cases of papillary thyroid carcinoma, which were immunohistochemically assessed for YAP1 and p53 expression. The study examined the association of their expression with clinicopathological characteristics.
Results: YAP1 expression was observed in 70% of papillary thyroid carcinoma cases. A statistically significant relation was observed between YAP1 expression and tumor size, tumor stage, tumor focality, lymph node metastases, and extrathyroidal extension (P-values were =0.003, > 0.001, 0.037, 0.025, and 0.006), respectively. p53 expression was observed in 85% of papillary thyroid carcinoma cases. A statistically significant relation was observed between p53 expression and tumor size (P=0.001) and tumor stage (P>0.001). A statistically significant relation was noticed between YAP1 and P53 expression (P=0.009).
Conclusion: YAP1 expression was found to be associated with many high-risk clinicopathological characteristics in patients with papillary thyroid carcinoma and with p53 expression; thus, it seems that YAP1 may have a specific impact on the patient's outcome.


Main Subjects

  1. Hernando J, Ros J, Arroyo A, Capdevila J. Clinical and translational challenges in thyroid cancer. Curr Med Chem. 2020;27(29):4806-22. [PMID] [DOI:10.2174/0929867327666200214125712]
  2. Freedman LS, Edwards BK, Ries LA, Young JL. Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER. Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER.. 2006.
  3. Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH. Papillary thyroid cancer: genetic alterations and molecular biomarker investigations. Int J Med Sci. 2019;16 (3):450. [DOI:10.7150/ijms.29935] [PMID] [PMCID]
  4. Zhu X, Yao J, Tian W. Microarray technology to investigate genes associated with papillary thyroid carcinoma. Molecul Med Rep. 2015;11(5):3729-33. [DOI:10.3892/mmr.2015.3180] [PMID]
  5. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;295(18):2164-7. [DOI:10.1001/jama.295.18.2164] [PMID]
  6. Todaro M BS, Mannino E, Stassi G. Role of IL-4 and IL-10 cytokines in the pathogenic mechanism of thyroid cancer. In: Milton CA, editor. Trends in Thyroid Cancer Research New York:2007. Nova Science Publishers Inc.pp33
  7. LiVolsi VA. Papillary thyroid carcinoma: an update. Mod Pathol. 2011;24(2):S1-9. [DOI:10.1038/modpathol.2010.129] [PMID]
  8. Porazinski S, Wang H, Asaoka Y, Behrndt M, Miyamoto T, Morita H, Hata S, Sasaki T, Krens SF, Osada Y, Asaka S. YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature. 2015;521(7551):217-21. [DOI:10.1038/nature14215] [PMID] [PMCID]
  9. Hagenbeek TJ, Webster JD, Kljavin NM, Chang MT, Pham T, Lee HJ, Klijn C, Cai AG, Totpal K, Ravishankar B, Yang N. The Hippo pathway effector TAZ induces TEAD-dependent liver inflammation and tumors. Sci Signal. 2018;11 (547):eaaj1757. [DOI:10.1126/scisignal.aaj1757] [PMID]
  10. Shibata M, Ham K, Hoque MO. A time for YAP1: Tumorigenesis, immunosuppression and targeted therapy. Int J Cancer. 2018 Nov 1;143(9):2133-44. [DOI:10.1002/ijc.31561] [PMID] [PMCID]
  11. Junttila MR, Evan GI. p53—a Jack of all trades but master of none. Nat Rev Cancer. 2009 Nov;9(11): 821-9. [DOI:10.1038/nrc2728] [PMID]
  12. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333-9. [DOI:10.1038/nature12634] [PMID] [PMCID]
  13. Huang K, Chen L, Zhang J, Wu Z, Lan L, Wang L, Lu B, Liu Y. Elevated p53 expression levels correlate with tumor progression and poor prognosis in patients exhibiting esophageal squamous cell carcinoma. Oncol Lett. 2014;8(4): 1441-6. [DOI:10.3892/ol.2014.2343] [PMID] [PMCID]
  14. Guimei M, Alrouh S, Saber-Ayad M, Hafezi SA, Vinod A, Rawat S, et al. Inhibition of Yes-associated protein-1 (YAP1) enhances the response of invasive breast cancer cells to the standard therapy. Breast Cancer: Targets Ther. 2020;12:189. [DOI:10.2147/BCTT.S268926] [PMID] [PMCID]
  15. Liu JY, Li YH, Lin HX, Liao YJ, Mai SJ, Liu ZW, e. Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder. BMC Cancer. 2013;13(1):1-8. [DOI:10.1186/1471-2407-13-349] [PMID] [PMCID]
  16. Lee YM, Lee JB. Prognostic value of epidermal growth factor receptor, p53 and galectin-3 expression in papillary thyroid carcinoma. J Int Med Res. 2013;41(3):825-34. [DOI:10.1177/0300060513477312] [PMID]
  17. Chang HY, Lin JD, Chou SC, Chao TC, Hsueh C. Clinical presentations and outcomes of surgical treatment of follicular variant of the papillary thyroid carcinomas. Jpn J Clin Oncol. 2006;36 (11):688-93. [DOI:10.1093/jjco/hyl093] [PMID]
  18. Guo L, Chen Y, Luo J, Zheng J, Shao G. YAP 1 overexpression is associated with poor prognosis of breast cancer patients and induces breast cancer cell growth by inhibiting PTEN. FEBS Open Bio. 2019;9(3):437-45. [DOI:10.1002/2211-5463.12597] [PMID] [PMCID]
  19. Zhou Q, Bauden M, Andersson R, Hu D, Marko-Varga G, Xu J, et al. YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling. J Transl Med. 2020;18(1):1-0. [PMID] [PMCID] [DOI:10.1186/s12967-020-02254-7]
  20. Wang X, Guo Y, Liu L, Wei J, Zhang J, Xie T, et al. YAP1 protein expression has variant prognostic significance in small cell lung cancer (SCLC) stratified by histological subtypes. Lung Cancer. 2021;160:166-74. [DOI:10.1016/j.lungcan.2021.06.026] [PMID]
  21. Cao L, Zhang C, Wu Q, Bai Z, Chen J. Yes‑associated protein expression is associated with poor prognosis in patients with colorectal cancer. Oncol Lett. 2021;22(3):1-9. [DOI:10.3892/ol.2021.12903] [PMID] [PMCID]
  22. Garcia-Rendueles ME, Ricarte-Filho JC, Untch BR, Landa I, Knauf JA, Voza F, et al. NF2 Loss Promotes Oncogenic RAS-Induced Thyroid Cancers via YAP-Dependent Transactivation of RAS Proteins and Sensitizes Them to MEK InhibitionNF2 Loss Transactivates Oncogenic RAS through YAP. Cancer Discov. 2015;5(11): 1178-93. [DOI:10.1158/2159-8290.CD-15-0330] [PMID] [PMCID]
  23. Lee SE, Lee JU, Lee MH, Ryu MJ, Kim SJ, Kim YK, et al. RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer. Oncogenesis. 2013;2(7):e55-. [DOI:10.1038/oncsis.2013.12] [PMID] [PMCID]
  24. Ugolini C, Borrelli N, Niccoli C, Elisei R, Viola D, Vitti P, Miccoli P, Basolo F. Role of YAP-1 in thyroid tumor progression and outcome. Appl Immunohistochem Mol Morphol. 2017 Sep 1;25(8):581-5. [DOI:10.1097/PAI.0000000000000344] [PMID]
  25. Liu Z, Zeng W, Maimaiti Y, Ming J, Guo Y, Liu Y, et al. High expression of yes-activated protein-1 in papillary thyroid carcinoma correlates with poor prognosis. Appl Immunohistochem Mol Morphol. 2019;27(1):59-64. [DOI:10.1097/PAI.0000000000000544] [PMID]
  26. Celano M, Mignogna C, Rosignolo F, Sponziello M, Iannone M, Lepore SM, et al. Expression of YAP1 in aggressive thyroid cancer. Endocrine. 2018;59(1):209-12. [DOI:10.1007/s12020-017-1240-6] [PMID]
  27. Liao T, Wen D, Ma B, Hu JQ, Qu N, Shi RL, et al. Yes-associated protein 1 promotes papillary thyroid cancer cell proliferation by activating the ERK/MAPK signaling pathway. Oncotarget. 2017 Feb 14;8(7):11719. [PMID] [PMCID] [DOI:10.18632/oncotarget.14319]
  28. Deyoung MP, Ellisen LW. p63 and p73 in human cancer: defining the network. Oncogene. 2007; 26(36):5169-83. [DOI:10.1038/sj.onc.1210337] [PMID]
  29. Gomes S, Leao M, Raimundo L, Ramos H, Soares J, Saraiva L. p53 family interactions and yeast: together in anticancer therapy. Drug Discov Today. 2016;21(4):616-24. [DOI:10.1016/j.drudis.2016.02.007] [PMID]
  30. 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 Sci. 2017;18(6):1325. [DOI:10.3390/ijms18061325] [PMID] [PMCID]
  31. Dwivedi SS, Khandeparkar SG, Joshi AR, Kulkarni MM, Bhayekar P, Jadhav A, et al. Study of immunohistochemical markers (CK-19, CD-56, Ki-67, p53) in differentiating benign and malignant solitary thyroid nodules with special reference to papillary thyroid carcinomas. J Clin Diagn Res. 2016;10(12):EC14. [PMID] [PMCID] [DOI:10.7860/JCDR/2016/22428.9114]
  32. Marcello MA, Morari EC, Cunha LL, De Nadai Silva AC, Carraro DM, Carvalho AL, Soares FA, Vassallo J, Ward LS. P53 and expression of immunological markers may identify early stage thyroid tumors. Clin Dev Immunol. 2013;2013. [DOI:10.1155/2013/846584] [PMID] [PMCID]
  33. Hosal SA, Apel RL, Freeman JL, Azadian A, Rosen IB, LiVolsi VA, et al. Immunohistochemical localization of p53 in human thyroid neoplasms: correlation with biological behavior. Endocrine Pathol. 1997;8(1): 21-8. [DOI:10.1007/BF02739704] [PMID]
  34. Shin MK, Kim JW. Clinicopathologic and diagnostic significance of p53 protein expression in papillary thyroid carcinoma. Asia Pac J Cancer Prev. 2014;15(5):2341-4. [DOI:10.7314/APJCP.2014.15.5.2341] [PMID]
  35. Morita N, Ikeda Y, Takami H. Clinical significance of p53 protein expression in papillary thyroid carcinoma. World J Surg. 2008;32 (12): 2617-22. [DOI:10.1007/s00268-008-9756-9] [PMID]
  36. Radu TG, Mogoantă L, Busuioc CJ, Stănescu C, Grosu F. Histological and immunohistochemical aspects of papillary thyroid cancer. Rom J Morphol Embryol. 2015;56(2 Suppl):789-95.
  37. Horie S, Maeta H, Endo K, Ueta T, Takashima K, Terada T. Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features. Pathol Int. 2001;51(1):11-5. [PMID] [DOI:10.1046/j.1440-1827.2001.01159.x]
  38. Sang W, Xue J, Su LP, Gulinar A, Wang Q, Zhai YY, et al. Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma. J Clin Pathol. 2021;74(8):513-21. [DOI:10.1136/jclinpath-2020-206868] [PMID]
  39. Di Agostino S, Sorrentino G, Ingallina E, Valenti F, Ferraiuolo M, Bicciato S, et al. YAP enhances the pro‐proliferative transcriptional activity of mutant p53 proteins. EMBO reports. 2016;17(2):188-201. [PMID] [PMCID] [DOI:10.15252/embr.201540488]
  40. Raj N, Bam R. Reciprocal crosstalk between YAP1/hippo pathway and the p53 family proteins: mechanisms and outcomes in cancer. Front Cell Dev Biol. 2019;7:159. [PMID] [PMCID] [DOI:10.3389/fcell.2019.00159]