Mesane ürotelyal karsinomlarında Cyclin-D1 immünohistokimyasal ekspresyonunun araştırılması

Amaç:Cyclin D1 hücre siklusunun düzenlenmesinde görev alan ve CCND1 geni tarafından kodlanan bir proteindir. Liteatürde Cyclin D1 ile ilgili az sayıda çalışma mevcut olup çalışmalarda sonuçlar farklılık göstermektedir. Bu çalışmada mesane üretelyal karsinomlarda Cyclin D1ekspresyonunun prognostik faktörler ile ilişkisi araştırıldı. Gereç ve Yöntem: Çalışmaya Kafkas Üniversitesi Sağlık Araştırma ve Uygulama Hastanesi’nde TUR-M yapılmış 46 olgu dahil edildi. Olgulara dair genel bilgiler ve patoloji raporları hastane otomasyon sisteminden elde edildi. Hazır boyalı patoloji preparatlarından tümör içeren kesitler seçilip seçilen kesitlere ait bloklara Cyclin D1 primer antikoru ile immunohistokimyasal boyama aşağıda belirtilen şekilde manuel olarak yapılmıştır.Boyanan kesitler ışık mikroskobunda nükleer ve sitoplazmik olarak ayrı ayrı 0-4 olarak skorlanarak değerlendirildi. Bulgular: Olguların yaş aralığı 51-93 olup ortalama yaş 69.2±11.7’dir. Olguların 12’si (%26.1) kadın, 34’ü (%73.9) erkektir. Histopatolojik bulgular incelendiğinde olguların 29’unun (%63.0) düşük dereceli 17’sinin (%37.0) yüksek dereceli olduğu gözlenmiştir. Olguların 18’i (%39.1) invaziv, 28’i (%60.9) noninvaziv niteliktedir. Yapılan istatistiksel analizlerde invazyon gösteren tümörlerin non-invaziv tümörlere göre (pTa) istatistiksel olarak anlamlı düzeyde yüksek dereceli olduğu dikkati çekmiştir (p= 0.007). Benzer şekilde invaziv tümörlerde lenfovasküler invazyon varlığı non-invaziv tümörlere göre istatistiksel olarak anlamlı derecede fazla saptanmıştır (p=0.001). Nükleer cyclin D1 expresyonunun (p=0.003) invaziv olgularda istatistiksel olarak anlamlı düzeyde daha yüksek olduğu izlenmiştir. Ayrıca düşük dereceli tümörlerde nükleer cyclinD1 ekspresyonu istatistisel olarak anlamlı düzeyde yüksek bulunduğu saptanmıştır (p=0.044). Sonuç: Çalışma sonucunda mesane üretelyal karsinomlu hastalarda Cyclin D1 ekspresyonun tümöe derecesi ve invazyon durumu ile ilişkisi gözlenmiştir ancak Cyclin D1’in biyobelirteç olarak kullanılabilmesi için daha geniş olgu serilerinde çalışmalara ihtiyaç duyulmaktadır.

Investigation of Cyclin-D1 immunohistochemical expression in bladder urethelial carcinoma

Objective: Cyclin D1 is a protein that is involved in the regulation of the cell cycle and is encoded by the CCND1 gene. There are few studies on Cyclin D1 in the literature, and the results differ in the studies. In this study, the relationship between Cyclin D1 Expression and prognostic factors in bladder urothelial carcinomas was investigated. Materials and Methods: Forty-six patients who underwent TUR-M at the Kafkas University Health Research and Application Hospital were included in the study. General information about the cases and pathology reports were obtained from the hospital automation system. Tumor-containing sections were selected from the ready-stained pathology preparations, and immunohistochemical staining was performed manually with Cyclin D1 primary antibody on the blocks of the selected sections, as indicated below. Stained sections were evaluated under the light microscope by scoring 0-4 separately as nuclear and cytoplasmic. Results: The age range of the cases was 51-93, and the mean age was 69.2±11.7. Twelve (26.1%) cases were female and 34 (73.9%) were male. When the histopathological findings were examined, it was observed that 29 (63.0%) of the cases were low-grade and 17 (37.0%) were high-grade. Eighteen (39.1%) of the cases were invasive and 28 (60.9%) were noninvasive. In the statistical analyzes performed, it was noted that invasive tumors had a statistically significantly higher grade compared to non-invasive tumors (pTa) (p= 0.007). Similarly, the presence of lymphovascular invasion in invasive tumors was statistically significantly higher than in non-invasive tumors (p=0.001). It was observed that nuclear cyclin D1 expression (p=0.003) was statistically significantly higher in invasive cases. In addition, nuclear cyclinD1 expression was found to be statistically significantly higher in low-grade tumors (p=0.044). Conclusion: As a result of the study, a relationship between Cyclin D1 expression and tumor grade and invasion status was observed in patients with bladder urethelial carcinoma, but studies with larger case series are needed to use Cyclin D1 as a biomarker.

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  • 1. Sayar İ. The Prognostic significance of the Cyclin D1/p16/Ki-67 markers in bladder urothelial carcinomas. Middle East Journal of Medicine. 2017;9(2):73-8. doi:10.21601/ortadogutipdergisi.265416.
  • 2. Siegel R, Naishadham D, Jemal A. Cancerstatistics, CA Cancer J Clin 2012;62(1):10-29. doi: 10.3322/caac.20138.
  • 3. Ren B, Li W, Yang Y, Wu, S. Theimpact of cyclin D1 overexpression on theprognosis of bladdercancer: a meta-analysis. World Journal of SurgicalOncology 2014;1:1. doi: 10.1186/1477-7819-12-55.
  • 4. Santos LL, Amaro T, Pereira SA, Lameiras CR, Lopes P, Bento MJ, et al. Expression of cell- cycleregulatory proteins and their prognostic value in superficiallow-grade urothelial cell carcinoma of the bladder. Eur J SurgOncol 2003;29:74-80. doi: 10.1053/ejso.2002.1371.
  • 5. Yurakh AO, Ramos D, Calabuig-Fariñas S, López-Guerrero JA, Rubio J, Solsona E, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycleregulators in urothelial neoplasms of the bladder. EurUrol 2006;50:506-515. doi: 10.21601/ortadogutipdergisi.265416.
  • 6. Eble JN, Young RH. Carcinoma of the urinary bladder: a review of its diver semorphology.Semin Diagn Pathol 1997;14:98–108. PMID: 9179971.
  • 7. Eble JN, Sauter G, Sesterhenn IA. Tumours of theUrinarySystem. In: Kleihues P, SobinLH. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. France: Lyon, IARC press, 2004: 89-158.
  • 8. Tiguert R, Lessard A, So A, Fradet Y. Prognostic markers in muscle invasive bladder cancer. World J Urol 2002;20:190–195. doi: 10.1007/s00345-002-0279-y.
  • 9. Ren B, Li W, Yang Y, Wu, S. The impact of cyclin D1 overexpression on the prognosis of bladder cancer: a meta analysis. World Journal of SurgicalOncology 2014;1:1. doi:10.21601/ortadogutipdergisi.265416.
  • 10. Krüger S, Mahnken A, Kausch I, Feller AC. P16 immunoreactivity is an in dependent predictor of tumor progression in minimally invasive urothelial bladder carcinoma. Eur Urol 2005;47:463-7. doi:10.1016/j.eururo.2004.12.018.
  • 11. Yurakh AO, Ramos D, Calabuig-Fariñas S, López-Guerrero JA, Rubio J, Solsona E, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur Urol 2006;50:506-15. doi:10.1371/journal.pone.0158891.
  • 12. Sgambato A, Migaldi M, Faraglia B, De Aloysio G, Ferrari P, Ardito R, De Gaetani C, Capelli G, Cittadini A, Trentini GP: Cyclin D1 expression in papillary superficial bladder cancer: it sassociation with other cell cycle-associated proteins, cell proliferation and clinical out come. Int J Cancer 2002, 97:671–678. doi:10.1159/000078807.
  • 13. Tut VM, Braithwaite KL, Angus B, Neal DE, Lunec J, Mellon JK: Cyclin D1 expression in transitional cellc arcinoma of the bladder: correlation with p53, waf1, pRband Ki67. Br J Cancer 2001, 84:270–275. doi:10.1054/bjoc.2000.1557.
  • 14. Takagi Y, Takashi M, Koshikawa T, Sakata T, Ohshima S: Immunohistochemical demonstration of cyclin D1 in bladder cancers as an inverseindicator of invasiveness but not an independent prognostic factor. Int J Urol 2000, 7:366–372. doi:10.1046/j.1442- 2042.2000.00212.x.
  • 15. Shin KY, Kong G, Kim WS, Lee TY, Woo YN, Lee JD: Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers. Br J Cancer 1997, 75:1788–1792. doi:10.1136/mp.51.1.1.
  • 16. Niehans GA, Kratzke RA, Froberg MK, Aeppli DM, Nguyen PL, Geradts J: G1 check point protein and p53 abnormal it iesoccur in most invasive transitional cell carcinomas of the urinary bladder. Br J Cancer 1999, 80:1175–1184. doi:10.1038/sj.bjc.6990483.
  • 17. Ploeg M, Aben KK, Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol 2009, 27:289–293. doi:10.1007/s00345-009-0383-3.
  • 18. Lee K, Jung ES, Choi YJ, Lee KY, Lee A. Expression of pRb, p53, p16 andcyclin D1 and their clinical implications in urothelial carcinoma. J Korean Med Sci 2010; 25: 1449-55. doi:10.3346/jkms.2010.25.10.1449.
  • 19. Kamalati T, Davies D, Titley J, Crompton MR. Functionalconsequence of cyclin D1 overexpression in human mammary luminal epithelial cells. Clin Exp Metastasis 1998:16;415- 426. doi:10.1023/a:1006529407652.
  • 20. Xu XL, Chen SZ, Chen W, Zheng WH, Xia XH, Yang HJ, Li B, Mao WM: The impact of cyclin D1 over expression on the prognosis of ER-positive breast cancers: a meta-analysis. Breast Cancer Res Treat 2013, 139:329–339. doi:10.1186/1477-7819-12-55.
  • 21. Alao JP: The regulation f cyclin D1 degradation: roles in cancer developmentand the potential for ther apeuticinvention. Mol Cancer 2007, 6:24. doi:10.1186/1476-4598-6-24.
  • 22. Fristrup N, Birkenkamp-Demtroder K, Reinert T, Sanchez-Carbayo M, Segersten U, Malmstrom PU, Palou J, Alvarez-Mugica M, Pan CC, Ulhoi BP, Borre M, Ørntoft TF, Dyrskjøt L: Multicentervalidation of cyclin D1, MCM7, TRIM29, and UBE2C as prognostic protein markers in non-muscle invasive bladder cancer. Am J Pathol. 2013,182:339–349. doi:10.18632/oncotarget.11277.
  • 23. Olsson H, Hultman P, Monsef N, Rosell J, Jahnson S: Immunohistochemical evaluation of cell cycle regulators: impact on predicting prognosis in stage t1 urinary bladder cancer. ISRN Urol 2012, 2012:379081. doi:10.5402/2012/379081.
  • 24. Behnsawy HM, Miyake H, Abdalla MA, Sayed MA, AhmedAel F, Fujisawa M: Expression of cellcycle-associated proteins in non-muscle-invasive bladder cancer: correlation with intravesical recurrence following transurethral resection. Urol Oncol 2011, 29:495–501. doi:10.1016/j.urolonc.2009.08.002.
  • 25. Lee K, Jung ES, Choi YJ, Lee KY, Lee A: Expression of pRb, p53, p16 andcyclin D1 and the clinical implications in urothelial carcinoma. J Korean Med Sci 2010, 25:1449–1455. doi:10.3346/jkms.2010.25.10.1449.
  • 26. Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y: Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with non muscle invasive urothelial cell carcinoma of the bladder. Urol Oncol 2007, 25:468–475. doi:10.1016/j.urolonc.2006.09.011.
  • 27. Lee, Eun Ju, et al. Aberrant methylation of Fragile Histidine Triad gene is associated with poor prognosis in early stage esophageal squamous cell carcinoma. European journal of cancer, 2006, 42.7: 972-980. doi:10.1016/j.ejca.2006.01.021
  • 28. Kopparapu, Pradeep Kumar, et al. Expression of cyclin d1 and its association with disease characteristics in bladder cancer. Anticancer research, 2013, 33.12: 5235-5242. doi:24324055
  • 29. Russell A, Thompson MA, Hendley J, Trute L, Armes J, Germain D. Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. Oncogene 1999; 18: 1983-91. doi: 10.1038/sj.onc.1202511
  • 30. Khabaz M.N., Buhmeida A., Ghabrah T., Qureshi I.A., Butt N.S., Al-Maghrabi B., Nedjadi T., AlQahtani M., Al-Maghrabi J. Cyclin D1 expression is associated with stage, grade and survival in urinary bladder carcinoma. Int J Clin Exp Med 2016;9, 23482-23490. doi:1087/328295.
  • 31. Sharıat, Shahrokh F., et al. Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. In: Urologic Oncology: Seminars and Original Investigations. Elsevier 2007; p. 468-475. doi: 10.1016/j.urolonc.2006.09.011
  • 32. Amer, Alaa Ibrahim; EID, Asmaa Mustafa. Prognostic significance of Cyclin D1 in urothelial carcinoma; correlation with p53 and clinicopathological parameters. J Am Sci, 2019, 15: 86- 91. doi:10.13668/sc.am.125448
  • 33. Kopparapu, Pradeep Kumar, et al. Expression of cyclin d1 and its association with disease characteristics in bladder cancer. Anticancer research 2013; 33.12: 5235-5242. doi:10.1371/0158891.
  • 34. Yan, Rongrong, et al. Overexpression of peptidyl-prolyl isomerase 1 (Pin1) and cyclin D1 in endometrial cancer. Int J Clin Exp Patho 2017;10: 3335-3343. doi: PMC4122540
  • 35. Yan, Rongrong, et al. Overexpression of peptidyl-prolyl isomerase 1 (Pin1) and cyclin D1 in endometrial cancer. Int J Clin Exp Patho, 2017, 10: 3335-3343.doi:10.1158/14785-240X-2
  • 36. Frıstrup, Niels, et al. Multicenter validation of Cyclin D1, MCM7, TRIM29, and UBE2C as prognostic protein markers in non-muscle–invasive bladder cancer. The American journal of pathology 2013;182.2: 339-349. doi: 10.1016/j.ajpath.2012.10.017
  • 37. Bahnassy, Abeer A., et al. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients. BMC gastroenterology 2004; 4.1: 1-12. doi: 10.1186/1471-230X- 4-22
Yeni Üroloji Dergisi-Cover
  • ISSN: 1305-2489
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2005
  • Yayıncı: Avrasya Üroonkoloji Derneği
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