The role of EZH2 and ARID1A in the diagnosis of flat urothelial lesions with atypia

Автор: Sameh Reham, Mostafa Naglaa Mostafa, Embaby Ahmed, Raouf Samar Abdel, Abdelwahab Khaled

Журнал: Сибирский онкологический журнал @siboncoj

Рубрика: Лабораторные и экспериментальные исследования

Статья в выпуске: 5 т.20, 2021 года.

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Background. Diagnosis of urothelial carcinoma in situ is of great importance because it has prognostic and therapeutic value. We aim to determine the utility of EZH2 and ARiD1A as a new tool in the diagnosis of carcinoma in situ. Material and Methods. This retrospective cross-sectional study included Twenty-four specimens of flat urothelial lesions, twenty specimens of CiS, and 10 of normal adjacent urothelium that was taken by cystoscopic resection biopsy procedure. immunohistochemical expression of EZH2 and ARiD1A. were evaluated in all studied cases. Results. All normal urothelium specimens showed high nuclear staining for ARiD1A and negative nuclear staining for EZH2. High EZH2 expression was observed in 80 % of CiS specimens compared to 20 % of flat urothelial lesions with atypia (p=0.001 ), while high ARiD1A expression was observed in 70.8 % of flat urothelial lesions with atypia compared to 25 % of CiS specimens (p=0.001). EZH2 was more accurate and specific in the diagnosis of carcinoma in situ. Conclusion. EZH2 and ARiD1A are promising diagnostic markers for urothelial CiS. EZH2 is more accurate and specific than ARiD1A in the diagnosis of carcinoma in situ versus other flat urothelial lesions.

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Dysplasia, carcinoma in situ, reactive atypia, immunohistochemistry

Короткий адрес: https://sciup.org/140261336

IDR: 140261336   |   DOI: 10.21294/18144861-2021-20-5-49-57

Список литературы The role of EZH2 and ARID1A in the diagnosis of flat urothelial lesions with atypia

  • Ferlay J., Colombet M., Soerjomataram I., Mathers C., Parkin D.M., Piñeros M., Znaor A., Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019 Apr 15; 144(8): 1941–1953. doi: 10.1002/ijc.31937.
  • Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov; 68(6): 394–424. doi: 10.3322/caac.21492.
  • Cheng L., Lopez-Beltran A., MacLennan G.T., Montironi R., Bostwick D.G. Neoplasms of the urinary bladder. Urologic Surgical Pathology. Elsevier, 2008. p. 258–351.
  • Humphrey P.A., Moch H., Cubilla A.L., Ulbright T.M., Reuter V.E. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul; 70(1): 106–119. doi: 10.1016/j.eururo.2016.02.028.
  • Moch H., Cubilla A.L., Humphrey P.A., Reuter V.E., Ulbright T.M.
  • The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol. 2016 Jul; 70(1): 93–105. doi: 10.1016/j.eururo.2016.02.029.
  • Nguyen J.K., Przybycin C.G., McKenney J.K., Magi-Galluzzi C. Immunohistochemical staining patterns of Ki-67 and p53 in florid reactive urothelial atypia and urothelial carcinoma in situ demonstrate significant overlap. Hum Pathol. 2020; 98: 81–88. doi: 10.1016/j.humpath. 2020.02.008.
  • Poropatich K., Yang J.C., Goyal R., Parini V., Yang X.J. Nuclear size measurement for distinguishing urothelial carcinomas from reactive urothelium on tissue sections. Diagn Pathol. 2016 Jun; 11(1): 57. doi: 10.1186/s13000-016-0501-7.
  • Lowenthal B.M., Sahoo D., Amin M.B., Hansel D.E. Urothelial Proliferation of Unknown Malignant Potential Involving the Bladder: Histopathologic Features and Risk of Progression in De Novo Cases and Cases With Prior Neoplasia. Arch Pathol Lab Med. 2020; 144(7): 853–62. doi: 10.5858/arpa.2019-0005-OA.
  • Cheng L., Zhang S., MacLennan G.T., Williamson S.R., Lopez-Beltran A., Montironi R. Bladder cancer: translating molecular genetic insights into clinical practice. Hum Pathol. 2011 Apr; 42(4): 455–81. doi: 10.1016/j.humpath.2010.07.007.
  • Takenaka A., Yamada Y., Miyake H., Hara I., Fujisawa M. Clinical outcomes of bacillus Calmette-Guérin instillation therapy for carcinoma in situ of urinary bladder. Int J Urol. 2008 Apr; 15(4): 309–13. doi: 10.1111/j.1442-2042.2008.02012.x.
  • Warrick J.I., Raman J.D., Kaag M., Bruggeman T., Cates J., Clark P., DeGraff D.J. Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer. Urol Oncol. 2016 Jun; 34(6): 258.e1-6. doi: 10.1016/j.urolonc.2016.02.011.
  • Pavlidou E.N., Balis V. Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes. World Acad Sci J. 2020; 2: 49–64. doi: 10.3892/wasj.2020.37.
  • Liu X., Wu Q., Li L. Functional and therapeutic significance of EZH2 in urological cancers. Oncotarget. 2017 Jun 6; 8(23): 38044–38055. doi: 10.18632/oncotarget.16765.
  • Kelso T.W.R., Porter D.K., Amaral M.L., Shokhirev M.N., Benner C., Hargreaves D.C. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. Elife. 2017 Oct 2; 6: e30506. doi: 10.7554/eLife.30506.
  • Suryo Rahmanto Y., Jung J.G., Wu R.C., Kobayashi Y., Heaphy C.M., Meeker A.K., Wang T.L., Shih Ie.M. Inactivating ARID1A Tumor Suppressor Enhances TERT Transcription and Maintains Telomere Length in Cancer Cells. J Biol Chem. 2016 Apr 29; 291(18): 9690–9. doi: 10.1074/jbc.M115.707612.
  • Luchini C., Veronese N., Solmi M., Cho H., Kim J.H., Chou A., Gill A.J., Faraj S.F., Chaux A., Netto G.J., Nakayama K., Kyo S., Lee S.Y., Kim D.W., Yousef G.M., Scorilas A., Nelson G.S., Köbel M., Kalloger S.E., Schaeffer D.F., Yan H.B., Liu F., Yokoyama Y., Zhang X., Pang D., Lichner Z., Sergi G., Manzato E., Capelli P., Wood L.D., Scarpa A., Correll C.U. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and metaanalysis. Oncotarget. 2015 Nov 17; 6(36): 39088–97. doi: 10.18632/oncotarget.5142.
  • Li J., Lu S., Lombardo K., Monahan R., Amin A. ARID1A alteration in aggressive urothelial carcinoma and variants of urothelial carcinoma. Hum Pathol. 2016 Sep; 55: 17–23. doi: 10.1016/j.humpath.2016.04.006.
  • Zhou X., Liu N., Zhang J., Ji H., Liu Y., Yang J., Chen Z. Increased expression of EZH2 indicates aggressive potential of urothelial carcinoma of the bladder in a Chinese population. Sci Rep. 2018 Dec; 8(1): 17792. doi: 10.1038/s41598-018-36164-y.
  • Kunju L.P., Lee C.T., Montie J., Shah R.B. Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia. Pathol Int. 2005 May; 55(5): 248–54. doi: 10.1111/j.1440-1827.2005.01821.x.
  • Lopez-Beltran A., Henriques V., Montironi R., Cimadamore A., Raspollini M.R., Cheng L. Variants and new entities of bladder cancer. Histopathology. 2019 Jan; 74(1): 77–96. doi: 10.1111/his.13752.
  • Cao Q., Wang C., Ding Y., Xu D., Qian S., Shen H., Qi J. ARID1A upregulation predicts better survival in patients with urothelial bladder carcinoma. J Int Med Res. 2020 Apr; 48(4): 300060519895687. doi: 10.1177/0300060519895687.
  • McKenney J.K., Desai S., Cohen C., Amin M.B. Discriminatory immunohistochemical staining of urothelial carcinoma in situ and nonneoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol. 2001 Aug; 25(8): 1074–8. doi: 10.1097/00000478-200108000-00013.
  • Ang P.P., Tan G.C., Karim N., Wong Y.P. Diagnostic Value of the EZH2 Immunomarker in Malignant Effusion Cytology. Acta Cytol. 2020; 64(3): 248–255. doi: 10.1159/000501406.
  • Raffone A., Travaglino A., Saccone G., Cieri M., Mascolo M., Mollo A., Insabato L., Zullo F. Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS. 2019 Sep; 127(9): 597–606. doi: 10.1111/apm.12977.
  • Raman J.D., Mongan N.P., Tickoo S.K., Boorjian S.A., Scherr D.S., Gudas L.J. Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder. Clin Cancer Res. 2005 Dec 15; 11(24 Pt 1): 8570–6. doi: 10.1158/1078-0432.CCR-05-1047.
  • Aso T., Uozaki H., Morita S., Kumagai A., Watanabe M. Loss of ARID1A, ARID1B, and ARID2 Expression During Progression of Gastric Cancer. Anticancer Res. 2015 Dec; 35(12): 6819–27.
  • Alldredge J.K., Eskander R.N. EZH2 inhibition in ARID1A mutated clear cell and endometrioid ovarian and endometrioid endometrial cancers. Gynecol Oncol Res Pract. 2017 Oct 31; 4: 17. doi: 10.1186/s40661-017-0052-y.
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