Mesane ürotelyal karsinomlarında Siklin D1/p16/Ki-67 belirteçlerinin prognostik önemi

ÖZAmaç: Ürotelyal karsinomların Siklin D1/p16/Ki-67 ekspresyonunu araştıran gerek ayrı ayrı ve gerekse ikili kombinasyonu ile yapılan az sayıda çalışmada sonuçlar farklılık göstermektedir. Bu çalışmada, mesane ürotelyal karsinomlarında Siklin D1/p16/Ki-67 belirteçlerinin patolojik prognostik faktörler ile ilişkisi araştırıldı. Yöntem ve gereç: Toplam 149 mesane ürotelyal karsinomu patoloji arşivinden seçildi. Tüm olgularda histopatolojik bulgular tekrar gözden geçirildi ve WHO/ISUP sistemine göre derecelendirme uygulandı. Her olgu için seçilen bir doku bloğuna Siklin D1/p16/Ki-67 için immünhistokimyasal boyama işlemi gerçekleştirildi.Bulgular: Siklin D1 boyanma oranı ilk pT evresi Ta-T1, düşük grade, rekürrens ve progresyon görülmeyen olgularda daha yüksek bulunmuştur. p16 boyanma oranı; yüksek grade, rekürrens görülen ve mortalite yüksek görülen olgularda anlamlı düzeyde yüksektir. Ki-67 boyanma oranı ise ilk pT evresi Ta-T1, düşük grade, rekürrens ve progresyon görülmeyen olgularda high (skor 3) görülme oranı, ilk pT evresi T2-T4, yüksek grade, rekürrens ve progresyon görülen olgulara göre anlamlı düzeyde düşüktür. Sonuç: Mesane ürotelyal karsinomlu hastalarda Siklin D1/p16/Ki-67 belirteçlerinin tümörün yüksek gradeliği ve rekürrensiyle istatistiksel olarak anlamlı bir birliktelik vardır. Siklin D1/p16/Ki-67 birlikteliği ürotelyal karsinomların progresyonunda ve diferansiyasyonunda rol oynayabilir.

Anahtar Kelimeler:

Ürotelyal Karsinom, Siklin D1, Ki-67

Prognostic significance of Cyclin d1 / p16 / Ki-67 markers in bladder urothelial carcinomas

Objectives: The results of a small number of studies on the expression of cyclin D1 / p16 / Ki-67 in urothelial carcinomas, either individually or in combination with each other, differ. In this study, the relationship between Cyclin d1 / p16 / Ki-67 markers in pathologic prognostic factors of bladder urothelial carcinoma was investigated.Materials and methods: A total of 149 bladder urothelial carcinomas were selected from the pathology archive. In all cases, histopathological findings were reviewed and graded according to the WHO / ISUP system. Immunohistochemical staining for Cyclin d1 / p16 / Ki-67 was performed on a selected tissue block for each case.Results: The rate of cyclin d1 staining was found to be higher in the first pT stage Ta-T1, low grade, recurrence and non-progressive cases. The rate of positivity is significantly higher in cases with high grade p16 staining, recurrence and high mortality. The Ki-67 staining rate is significantly lower than the first pT stage Ta-T1, low grade, high (score 3) incidence in cases without recurrence and progression, first pT stage T2-T4, high grade, recurrence and progression. Conclusion: Cyclin d1 / p16 / Ki-67 markers in patients with bladder urothelial carcinoma have a statistically significant association with tumor grade and recurrence. Cyclin d1 / p16 / Ki-67 association may play a role in the progression and differentiation of urothelial carcinomas.

Keywords:

Urothelial carcinoma, Cyclin D1, Ki- 67,

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1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62(1):10-29.
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
3. Tadin T, Krpina K, Stifter S, Babarovic E, Fuckar Z, Jonjic N. Lower cyclooxygenase-2 expression is associated with recurrence of solitary non-muscle invasive bladder carcinoma. Diagn Pathol 2012;7:152.
4. Goyal S, Singh UR, Sharma S, Kaur N. Correlation of mitotic indices, AgNor count, Ki-67 and Bcl-2 with grade and stage in papillary urothelial bladder cancer. Urol J 2014;11:1238-1247.
5. Niehans GA, Kratzke RA, Froberg MK, Aeppli DM, Nguyen PL, Geradts J: G1 checkpoint protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder. Br J Cancer 1999;80:1175-1184.
6. Strauss M, Lukas J, Bartek J: Unrestricted cell cycling and cancer. Nat Med 1995;1:1245-1246.
7. Raspollini MR, Minervini A, Lapini A, Lanzi F, Rotellini M, Baroni G, et al. A proposed score for assessing progression in pT1 high-grade urothelial carcinoma of the bladder. Appl Immunohistochem Mol Morphol 2013;21:218-227.
8. Salehinejad J, Sharifi N, Amirchaghmaghi M, Ghazi N, Shakeri MT, Ghazi A. Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus. Ann Diagn Pathol 2014;18:210-213.
9. Rawish KR, Desouki MM, Crispens MA, Fadare O. Conventional endometrioid adenocarcinomas of the endometrium recurring as clear cell tumors: comparative immunohistochemical analyses. Ann Diagn Pathol 2013;17(3):270-275.
10. van Bogaert LJ. P16INK4a immunocytochemistry/immunohistochemistry: need for scoring uniformization to be clinically useful in gynecological pathology. Ann Diagn Pathol 2012;16:422-426.
11. Chatterjee SJ, George B, Goebell PJ, Alavi Tafreshi M, Shi SR, Fung YK, et al. Hyperphosphorylation of pRb: a mechanism for RB tumour suppressor pathway inactivation in bladder cancer. J Pathol 2004;203:762-770.
12. Ding W, Gou Y, Sun C, Xia G, Wang H, Chen Z, et al. Ki-67 is an independent indicator in non-muscle invasive bladder cancer (NMIBC); combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC. Urol Oncol 2014;32:(42)13-19.
13. Pich A, Chiusa L, Formiconi A, Galliano D, Bortolin, P, Comino A et al. Proliferative activity is the most significant predictor of recurrence in noninvasive papillary urothelial neoplasms of low malignant potential and grade 1 papillary carcinomas of the bladder. Cancer 2002;95:784-790.
14. Sgambato A, Migaldi M, Faraglia B, De Aloysio G, Ferrari, P, Ardito R, et al. Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. Int J Cancer 2002;97(5):671-678.
15. Sugianto J, Sarode V, Peng Y. Ki-67 expression is increased in p16-expressing triple-negative breast carcinoma and correlates with p16 only in p53-negative tumors. Hum Pathol 2014; 45(4): 802-809.
16. Wang L, Feng C, Ding G, Zhou Z, Jiang H, Wu Z. Relationship of TP53 and Ki67 expression in bladder cancer under WHO 2004 classification J BUON 2013;18(2): 420-424.
17. Fahmy M, Mansure JJ, Brimo F, Yafi FA, Segal R, Althunayan A, et al. Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer. Hum Pathol 2013;44(9):1766-1772.
18. Reed JC. Dysregulation of apoptosis in cancer. J Clin Oncol 1999;17(9):2941-2953.
19. Baumgart E, Cohen MS, Silva Neto B, Jacobs MA, Wotkowicz C, Rieger-Christ KM, et al. Identificationand prognostic significance of an epithelial-mesenchymal transitionexpression profile in human bladder tumors. Clin Cancer Res 2007; 13:1685-1694.
20. Shariat SF, Bolenz C, Karakiewicz PI, Fradet Y, Ashfaq R, Bastian PJ, et al. p53 expression in patients with advanced urothelial cancer of the urinary bladder. BJU Int 2010;105:489-495.
21. Fauconnet S, Bernardini S, Lascombe I, Boiteux G, Clairotte A, Monnien F, et al. Expression analysis of VEGF-A and VEGF-B: relationship with clinicopathological parameters in bladder cancer. Oncol Rep 2009;21:1495-1504.
22. 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 Surgical Oncology 2014;1:1.
23. Krüger S, Mahnken A, Kausch I, Feller AC. P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma. Eur Urol 2005;47:463-467.
24. Bartoletti R, Cai T, Nesi G, Girardi LR, Baroni G, Dal Canto M. Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer. J Surg Res 2007;143: 422-427.
25. Santos LL, Amaro T, Pereira SA, Lameiras CR, Lopes P, Bento MJ, et al. Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder. Eur J Surg Oncol 2003;29:74-80.
26. 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;50:506-515.