Böbreğin renal hücreli karsinomlarında Ki-67 proliferasyon indeksi, p53 expresyonu, AgNOR sayısı ve prognostik faktörlerin, histopatolojik tip ve derecelendirme ile ilişkisi

Amaç: En sık görülen malign böbrek tümörü olan renal hücreli karsinomlar, ürolojik tümörler içerisinde 3. sıradadır. Renal hücreli karsinomu olan hastalar genellikle kötü prognoza sahiptir. Bu çalışmamızda, renal hücreli karsinomlu olgulara ait nefrektomi materyallerinden hazırlanan örneklerde, immünhistokimyasal olarak P53 ve Ki-67, histokimyasal olarak AgNOR'un boyanma özelliklerini karşılaştırarak, bunların prognostik kriterler olarak yararının değerlendirilmesi amaçlandı. Gereç ve Yöntemler: 1994-2002 yılları arasında Renal hücreli karsinom tanısı alan nefrektomi materyalleri çalışmaya alındı. Toplam 54 olgunun tanıları doğrulandı. Prognostik faktörler yeniden değerlendirildi. İmmünohistokimyasal olarak Ki-67, P53 ve AgNOR boyama yöntemi uygulandı. Bulgular: Ki-67 PI şeffaf RCC'de %4.55, granüler RCC'de %3.33, kromofob RCC'de %3.66, iğsi hücreli karsinomda %28.7, kistik RCC'de %0.3 olarak belirlendi ve Ki-67 PI'nin renal hücreli karsinomlarda histopatolojik tiplere göre değişiklikler gösterdiği saptandı. İğsi RCC'nin PI'si ile diğer tip RCC'lerin PI'leri arasında anlamlı bir farklılık bulunmaktaydı (P

The relationship of Ki-67 proliferation index, p53 expression, AgNOR number and prognostic factors in kidney's renal cell carcinomas with histopathological type and grading

Objective: Renal cell carcinomas, the most common malignant kidney tumor, ranks third among urological tumors. The patients with renal cell carcinoma usually have bad prognosis. In this study, in the samples prepared by nephrectomy materials belonging to incidents with renal cell carcinoma, by comparing P53 ve Ki-67 immunohistochemically, AgNOR's chromophobe qualities histochemically, it was aimed to evaluate the benefit of them as prognostic criteria. Materials and Methods: Nephrectomy materials diagnosed with renal cell carnicoma were taken into study between 1994 and 2002 in our department. Sections of 54 incidents were looked into and diagnoses were confirmed. Prognostic factors were re-evaluated. Ki-67 P53 and AgNOR chromophobe methods were applied to the prepared sections as immunohistochemically. Results: Ki-67 PI was determined to be 4.55% in transparent RCC, 3,33% in granular RCC, 3,66%in chromoplobe RCC, 28,7% in fusiform cell carcinoma,0,3% in cystic RCC, and it was found out that Ki-67 PI displayed differences according to histopathological types in renal cell carnicomas. There was a significant difference between PI of fusiform RCC and PI of other types of RCC (p<0.001). Conclusion: In conclusion, we decided to that the parameters as prognostic factors, because of studies showing differences between the reliability in determining the prognosis was not enough.

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1) Papadopoulos I,Rudolph P, Weichert-Jacopsen K.Value of p53 Expression, Cellular Proliferation, and DNA Content as Prognostic Indicators in Renal Cell Carcinoma. Eur Urol 1997; 32:110-117.
2) Papadopoulos I, Weichert-Jacobsen K, Sprenger E, Wacker H.H. DNA Content and the Proliferation Marker Ki-67 as Prognostic İndicators in Renal Cell Carcinoma.Urol Int 1994; 53:181-185.
3) Ordonez NG, Rosai J. Ürinary tract. Rosai J (editör). Ackerman's Surgical Pathology. Eighth Edition, St. Louis: Missouri: Mosby Year Book Inc, 1996: 1059-1184.
4) Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Syrjänen K. Prognostic Value of Ki-67 Expression in Renal Cell Carcinoma. Eur Urol 1997;31:350-355.
5) Shımazuı T, Tomobe M, Hattorı K, Uchida K, Akaza H, Koıso K. A Prognostic Sıgnıfıcance Of Nucleolar Organizer Region (AgNOR) In Renal Cell Carcinoma. J Urol 1995;154:1522-1526.
6) Visapaa H, Bui M, Huang Y at al. Correlation of Ki-67 and gelsolin expression to clinical outcome in renal cell carcinoma. Urology 2003; 61: 845-850.
7) Lang H, Jacqmin D. Prognostic factors in renal cell carcinoma. EAU Update series. 2003; 1: 215-219.
8) De la Taille A, Buttyan R, Katz AE at al. Biomarkers of renal cell carcinoma past and future considerations. Urol Oncol 2000; 5: 139-148.
9) Yasunaga Y, Shin M, Miki T, Okuyama A, Aozasa K. Prognostic factors of renal cell carcinoma: a multivariate analysis. J surg oncol 1998; 68: 11-18.
10) Delahunt B. Histopathologic prognostic indicators for renal cell carcinoma. Seminn diagn pathol 1998;15: 68-76.
11) Moch H, Gasser T, Amin MB, Torhorst J, Sauter G, Mihatsch MJ. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma. Cancer 2000; 89: 604-614.
12) Bugert P, Kovacs G. Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis. Am J Pathol 1996; 149: 2081-2088.
13) Bostwick D, Eble J, Denis L, Murphy G, Von Eschenbach A. Diagnosis and prognosis of renal cell carcinoma. Cancer 1997;80: 973-1001.
14) Girgin C, Tahran H, Hekimgil M, Sezer A, Gürel G. P53 Mutations and Other Prognostic Factors of Renal Cell Carcinoma. Urol Int 2001; 66: 78-83.
15) Goldstein NS. Grading of renal cell carcinoma. Urol Clin Nort Am 1999; 26: 637-642.
16) Gelb AB, Sudilovsky D, Wu DC, Weiss LM, Mederios LJ. Appraisal of İntratumoral Microvessel Density, MIB-1 Score, DNA Content and p53 Protein Expression as Prognostic Indicators in Patients with Locally Confined Renal Cell Carcinoma. American Cancer Society 1997; 1768-1775.
17) Tomita Y, Bilim V, Kawasaki Tat al. Frequent Expression of Bcl-2 in Renal Cell Carcinomas Carrying Wild-Type p53. Int. J. Cancer 1996;66: 322-325.
18) Sejima T, Miyagawa I. Expression of Bcl-2, p53 Oncoprotein and Proliferating Cell Nuclear Antigen in Renal Cell Carcinoma. Eur Urol 1999;35: 242-248.
19) Haitel A, Wiener HG, Blaschitz U, Marberger M, Susani M. Biologic Behavior of and p53 Overexpression in Multifocal Renal Cell Carcinoma of Clear Cell Type. Cancer 1999; 85:1593-1598.
20) Vasavada PS, Novick AC, Williams B. P53, bcl-2 and Bax Expression in Renal Cell Carcinoma. Urology 1998; 1057-1061.
21) Patard JJ, Leray E, Rodriguez A, Leclercq NR, Guille F, Lobel B. Correlation between symptom graduation, tumor characteristics and survival in renal cell carcinoma. Eur Urol 2003; 44: 226-232.
22) Gelb AB. Renal cell carcinoma. Cancer 1997; 80: 981-986.
23) Ficarra V, Righetti R, Pilloni Sat al. Prognostic factors in patients with renal cell carcinoma: Retrospective analysis of 675 cases. Eur Urol 2002; 41: 190-198.
24) Gerdes J, Li L, Schlueter Cat al. Immunobiochemical and moleculer biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 1991; 138: 867-873.
25) Munakata S, Hendricks JB. Effect of fixation time and microwave oven heating time on retrieval of the Ki-67 antigen from paraffin-embedded tissue. J Histochem Cytochem 1993; 41: 1241-1246.
26) Tsuji M, Kojima K, Murakami Y, Kanayama H, Kagawa S. Prognostic value of Kİ-67 antigen and p53 protein in urinary bladder cancer: Immunohistochemical analysis of radical cystectomy specimens. Br J Urol 1997; 79: 367-372.
27) Delahunt B, Bethwaite P, Thornton A, Ribas JL. Proliferation of renal cell carcinoma assessed by fixation resistant polyclonal Ki-67 antibody labeling: Correlation with outcome. Cancer 1995; 75: 2714-2719.
28) Key G, Becker MHG, Baron B, Duchrow M, Schluter C, Flad HD, Gerdes J. New Ki-67 equivalent murine monoklonal anti-bodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetative elements encoding for the Ki-67 epitope. Lab Invest 1993; 68: 629-636.
29) Tannapfel A, Hahn HA, Katalinic A, Fietkau RJ, Kuhn R, Wittekind R. Incidence of Apoptosis, Cell Proliferation and p53 Expression in Renal Cell Carcinomas. Anticancer Res 1997; 17: 1155-1162.
30) Bot FJ, Godschalk JC, Krishnadth KK, Van Der Kwast T, Bosman FT. Prognostic Factors in Renal Cell Carcinoma: Immunohistochemical Detection of p53 Protein Versus Clinocopathological Parameters. Int. J. Cancer 1994; 57: 634-637.
31) Rioux-Leclerq N, Turlin B, Bansard JY at al. Value of Immunohistochemical Ki-67 and p53 Determination as Predictive Factors of Outcome in Renal Cell Carcinoma. Urology 2000; 55: 501-505.
32) Tannapfel A, Hahn HA, Katalinic A, et al. Prognostic value of ploidy and proliferation markers in renal cell carcinoma. Cancer 1996; 77: 164-171.
33) Di Stefano D, Mingazzini PL, Scuchi L, Donetti M, Marinozzi V. A Comparative study of histopathology, hormone receptors, peanut lectin binding, Ki-67 immunstaining and nucleolar organizer region associated proteins in human breast cancers. Cancer 1991; 67: 463-471.
34) Leek RD, Alison MR, Sarraf CE. Variation in the occurrence of silver staining nucleolar organizer regions (AgNOR) in non proliferating tissues. J Pathol 1991; 165:43-51.
35) Pich A, Chiusa L, Margaria E. Prognostic relevance of AgNORs in tumor pathology. Micron 2000; 31: 133-141.
36) Delahunt B, Bethwaite PB, Nacey JN, Ribas JL. Proliferating cell nuclear antigen (PCNA) expression as a prognostic indicator for renal cell carcinoma: comparison with tumour grade, mitotic index, and silver- staining nucleolar organizer region numbers. J pathol 1993; 170: 471-477.
37) Ulhman DL, Nguyen PL, Manivel JC at al. Assocation of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma. J Natl Cancer Inst 1994; 86: 1470-1475.