COEXISTENCE OF CD44 AND KI-67 AS THE PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA

Year 2020, , 79 - 88, 30.04.2020

Tuba Devrim , Mahi Balcı

https://doi.org/10.24938/kutfd.671178

Cited By: 2

Abstract

Objective: An important feature of renal cell carcinoma (RCC) is its changeable prognosis. In recent years, several potential biomarkers have been investigated and confirmatory studies of these promising biomarkers are necessary to improve the clinical practice. In the present study, it was aimed to investigate the prognostic significance of CD44 expression by comparing it with Ki-67 and p53 in clear cell RCC.

Material and Methods: Formalin- fixed, paraffin-embedded tissue sections of clear cell RCC from 34 patients, who had undergone radical or partial nephrectomy, were included in this study. Correlations between CD44, Ki-67 and p53 immunohistochemical expressions and clinicopathological parameters were determined.

Results: CD44-high expression group (HEG) was significantly associated (p=0.035) and correlated (p=0.016, r=0.41) with a high nuclear grade. Similarly, the Ki-67-HEG was significantly associated (p=0.01) and correlated (p=0.01, r=0.436) with a high nuclear grade. We also found significant association (p<0.01) and correlation (p<0.01, r=0.621) between expressions of these markers. However, no antigen-antibody interaction was detected by p53 staining in clear cell RCC tissue sections.

Conclusion: We concluded that increased expressions of CD44 and Ki-67 in tumour tissues predict an aggressive course of RCC patients.

Keywords

Renal cell carcinoma, clear cell, CD44, Ki-67, p53

Renal Hücreli Karsinomda Prognostik Belirteçler Olarak CD44 ve Ki-67 Birlikteliği

Abstract

Amaç: Renal hücreli karsinomun (RHK) önemli bir özelliği değişen prognozudur. Son yıllarda, birkaç potansiyel biyobelirteç araştırılmış olup ve bu umut verici biyobelirteçlere ait doğrulayıcı çalışmalar klinik uygulamayı geliştirmek için gereklidir. Bu çalışmada, berrak hücreli RHK'de CD44 ekspresyonunun prognostik öneminin, Ki-67 ve p53 ile karşılaştırarak araştırılması amaçlandı.

Gereç ve Yöntemler: Radikal veya parsiyel nefrektomi yapılan 34 hastanın berrak hücreli RHK'nin formalinle fikse edilmiş, parafine gömülü doku kesitleri çalışmaya dahil edildi. CD44, Ki-67 ve p53 immünohistokimyasal ekspresyonları ve klinikopatolojik parametreler arasındaki korelasyonlar belirlendi.

Bulgular: CD44-yüksek ekspresyon grubu (HEG) ile yüksek nükleer derece arasında anlamlı bir ilişki (p=0.035) ve korelasyon saptandı (p=0.016, r = 0.41). Benzer şekilde, Ki-67-HEG ile yüksek nükleer derece arasında önemli bir ilişki (p=0.01) ve korelasyon saptandı (p=0.01, r=0.436). Ayrıca bu iki belirteç arasında anlamlı ilişki (p<0.01) ve korelasyon (p<0.01, r=0.621) bulundu. Bununla birlikte, berrak hücreli RHK doku kesitlerinde p53 immünhistokimyasal boyanması saptanmadı.

Sonuç: Tümör dokularında artmış CD44 ve Ki-67 ekspresyonlarının, RHK hastalarında agresif bir seyiri öngördüğü sonucuna vardık.

Keywords

Renal hücreli karsinom, berrak hücreli, CD44, Ki-67, p53, p53

References

• 1. Moch H, Humphrey PA, Ulbright TM, Reuter VE. World Health Organization (WHO) classification of tumours. Pathology and genetics of the urinary system and male genital organs. 4th ed. Geneva. WHO Press, 2016.
• 2. Gorin MA, Allaf ME. Diagnosis and Surgical Management of Renal Tumors. Springer, Cham, 2019.
• 3. Isik U, Kostek O, Demiray G, Dirican A, Simsek M, Buyuksimsek M et al. Real-life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer. J Clin Oncol. 2019;37(15):e16075.
• 4. Barrisford GW, Singer EA, Rosner IL, Linehan WM, Bratslavsky G. Familial renal cancer: molecular genetics and surgical management. Int J Surg Oncol. 2011;2011:658767.
• 5. Farber NJ, Kim CJ, Modi PK, Hon JD, Sadimin ET, Singer EA. Renal cell carcinoma: the search for a reliable biomarker. Transl Cancer Res. 2017;6(3):620-32.
• 6. Sato T, Kawasaki Y, Maekawa M, Takasaki S, Saigusa D, Ota H et al. Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma. Int J Cancer. 2019;145(2):484-93.
• 7. Domev H, Amit M, Laevsky I, Dar A, Itskovitz-Eldor J. Efficient engineering of vascularized ectopic bone from human embryonic stem cell-derived mesenchymal stem cells. Tissue Eng Part A. 2012;18(21-22):2290-302.
• 8. Yin T, Wang G, He S, Liu Q, Sun J, Wang Y. Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells. Cell Immunol. 2016;300:41-5.
• 9. Costa WH, Rocha RM, Cunha IW, Guimaraes GC, Zequi Sde C. Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent prognostic significance. Int Braz J Urol. 2012;38(4):456-65.
• 10. Luo Y, Zhang X, Mo M, Tan Z, Huang L, Zhou H et al. High Ki-67 immunohistochemical reactivity correlates with poor prognosis in bladder carcinoma: a comprehensive meta-analysis with 13,053 patients involved. Medicine (Baltimore). 2016;95(15):e3337.
• 11. Xie Y, Chen L, Ma X, Li H, Gu L, Gao Y et al. Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis. Sci Rep. 2017;7:44281.
• 12. Zheng K, Zhu W, Tan J, Wu W, Yang S, Zhang J et al. Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma. J Buon. 2014;19(2):512-6.
• 13. Gontero P, Ceratti G, Guglielmetti S Andorno A, Terrone C, Bonvini D et al. Prognostic factors in a prospective series of papillary renal cell carcinoma. BJU Int J. 2008;102(6):697-702.
• 14. Wang Z, Peng S, Jiang N, Wang A, Liu S, Xie H et al. Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis. Oncotarget. 2017;8(60):102361-370.
• 15. Santoro A, Vlachou T, Luzi L, Melloni G, Mazzarella L, D’Elia E et al. p53 loss in breast cancer leads to myc activation, increased cell plasticity, and expression of a mitotic signature with prognostic value. Cell Rep. 2019;26(3):624-38.
• 16. Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell. 2007;12(4):303-12.
• 17. Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA. 2005;102(38):13550-5.
• 18. Zhang F, Xie Y, Ma X, Gu L, Li H, Li X et al. Preoperative apolipoprotein B/A1 ratio is an independent prognostic factor in metastatic renal cell carcinoma. Urol Oncol. 2019;37(3):184.e9-e17.
• 19. College of American Pathologists (CAP). Accessed date: 6 January 2020: https://documents.cap.org/protocols/cp-kidney-17protocol-4011.pdf.
• 20. Chakraborty B, Sarkar P, Bhattacharya P, Ghosh T, Maiti K. Correlation of vascular endothelial growth factor (VEGF) and Ki-67 expression with histological grade and stage of renal cell carcinoma. J Evolution Med Dent Sci. 2019;8(10):706-11.
• 21. Menon SS, Guruvayoorappanb C, Sakthivelc KM, Rasmid RR. Ki-67 protein as a tumour proliferation marker. Clinica Chimica Acta. 2019;491:39-45.
• 22. Mehdi MZ, Nagi AH, Naseem N. MCM-2 and Ki-67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis. Int Braz J Urol. 2016;42(6):1121-8.
• 23. Gayed BA, Youssef RF, Bagrodia A, Darwish OM, Kapur P, Sagalowsky A et al. Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma. BJU Int J. 2014;113(4):668-73.
• 24. Toma MI, Weber T, Meinhardt M, Zastrow S, Grimm MO, Füssel S et al. Expression of the Forkhead Transcription Factor FOXP1 is Associated with Tumor Grade and Ki67 Expression in Clear Cell Renal Cell Carcinoma. Cancer Invest. 2011;29(2):123-9.
• 25. Wong PK, Lee ST, Murone C, Eng J, Lawrentschuk N, Berlangieri SU et al. In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET. Asia Ocean J Nucl Med Biol. 2014;2(1):3-11.
• 26. Amouian S, Farzadnia M, Memar B, Attaranzadeh A, Tayyebi N. Expression of P53 and Ki67 proteins in renal cell carcinoma and its relationship with nuclear grade. Iranian J Pathol. 2008;3(1):25-9.
• 27. Delahunt B, Bethwaite PB, Thornton A, Ribas JL. Proliferation of renal cell carcinoma assessed by fixation‐resistant polyclonal Ki‐67 antibody labeling. Correlation with clinical outcome. Cancer. 1995;75(11):2714-9.
• 28. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12(2):133-43.
• 29. Zanjani LS, Madjd Z, Abolhasani M, Rasti A, Fodstad O, Andersson Y et al. Increased expression of CD44 is associated with more aggressive behavior in clear cell renal cell carcinoma. Biomark Med. 2018;12(1):45-61.
• 30. Lim SD, Young AN, Paner GP, Amin MB. Prognostic role of CD44 cell adhesion molecule expression in primary and metastatic renal cell carcinoma: a clinicopathologic study of 125 cases. Virchows Archiv. 2008;452(1):49-55.
• 31. Qin J, Yang B, Xu BQ, Smithc A, Xu L, Yuan JL et al. Concurrent CD44s and STAT3 expression in human clear cell renal cellular carcinoma and its impact on survival. Int J Clin Exp Pathol. 2014;7(6):3235-44.
• 32. Uchino M, Kojima H, Wada K, Imada M, Onoda F, Satofuka H et al. Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells. BMC Cancer. 2010;10:414.
• 33. Li X, Ma X, Chen L, Gu L, Zhang Y, Zhang F et al. Prognostic value of CD44 expression in renal cell carcinoma: a systematic review and meta-analysis. Sci Rep. 2015;19(5):13157.
• 34. Jeong BJ, Liang Z, Huang SM, Lim JS, Kim JM, Lee HJ. CD44 is associated with tumor recurrence and is an independent poor prognostic factor for patients with localized clear cell renal cell carcinoma after nephrectomy. Exp Ther Med. 2012;3(5):811-7.
• 35. Warburton HE, Brady M, Vlatković N, Linehan WM, Parsons K, Boyd MT. p53 Regulation and Function in Renal Cell Carcinoma. Cancer Res. 2005;65(15):6498-503.
• 36. Haitel A, Wiener HG, Baethge U, Marberger M, Susani M. MDM2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters. Clin Cancer Res. 2000;6(5):1840-4.
• 37. Zigeuner R, Ratschek M, Rehak P, Schips L, Langner C. Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue. Urol. 2004;63(4):651-5.
• 38. Kang JH, Lee SH, Cheong H, Lee CH, Kim SY. Transglutaminase 2 promotes autophagy by LC3 induction through p53 depletion in cancer cell. Biomol Ther (Seoul). 2019;27(1):34-40.
• 39. Knezović Florijan M, Ozretić P, Bujak M, Pezzè L, Ciribilli Y, Kaštelan Ž et al. The role of p53 isoforms' expression and p53 mutation status in renal cell cancer prognosis. Urol Oncol. 2019;37(9):578.e1-578.e10.
• 40. Noroozinia F, Fahmideh AN, Yekta Z, Rouhrazi H, Rasmi Y. Expression of CD44 and P53 in renal cell carcinoma: association with tumor subtypes. Saudi J Kidney Dis Transpl. 2014;25(1):79-84.
• 41. Mombini H, Givi M, Rashidi I. Relationship between expression of p53 protein and tumor subtype and grade in renal cell carcinoma. Urol J. 2006;3(2):79-81.