DOI: http://dx.doi.org/10.18203/2349-2902.isj20194425

Expression of proliferating cell nuclear antigen and Ki-67 in renal cell carcinoma in eastern Indian patients

Sandip Pramanik, Subhayan Sur, Biswabandhu Bankura, Chinmay Kumar Panda, Dilip Kumar Pal

Abstract


Background: Several molecular markers play important role in development and prognosis of renal cell carcinoma (RCC). Proliferating cell nuclear antigen (PCNA) and Ki-67 are such kind of molecular markers which may have prognostic significance in RCC and need to be studied about. Estimation of proliferation index by immunohistochemical expression analysis of PCNA and Ki-67 at different clinical stages of RCC samples and correlations of expression of the genes with different clinicopathological parameters between tumour tissue cells and adjacent normal tissue cells were the objectives.

Methods: Thirty two patients of RCC who had been operated at one tertiary care institute of eastern India were taken for the study. Histopathological and immunohistochemistry analysis of PCNA and Ki-67 from tumour tissue and normal tissue were done. Patients who received radiotherapy, chemotherapy etc. before operation and who had benign tumours of the kidney in histopathological examination were excluded from the study.

Results: Mean PCNA expression in normal renal tissue is 4.54%; whereas the clear cell RCC, papillary RCC and chromophobe RCC showed 49.81%, 50.75% and 66.50% of mean PCNA expression respectively. Mean expression of Ki-67 in normal tissues was 1.75%. Whereas the clear cell RCC, papillary RCC and chromophobe RCC showed 23.96%, 24.75% and 31% of mean Ki-67 expression respectively. Both molecular markers were positively correlated overall.

Conclusions: PCNA and Ki-67 expression is increased in RCC when compared with normal tissues and it increases with Stage of RCC. PCNA expression is positively correlated with Ki-67 in different stages and histopathological groups of RCC. 


Keywords


PCNA, Ki-67, Renal cell carcinoma

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References


Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin. 1999;49:8-31.

Yuan ZX, Mo J, Zhao G, Shu G, Fu HL, Zhao W, Targeting strategies for renal cell carcinoma:from renal cancer cells to renal cancer stem cells. Front Pharmacol. 2016;7:1-15.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11-30.

Cook A, Lorenzo AJ, Salle JL, Bakhshi M, Cartwright LM, Bagi D, et al. Pediatric renal cell carcinoma:single institution 25-year case series and initial experience with partial nephrectomy. J Urol. 2006;175:1456-60.

Störkel S. Classification of renal cancer: Correlation of morphology and cytogenetics. Vogelzang NJ Scardino PT, Shipley WU, Coffey DS, eds. Comprehensive textbook of genitourinary oncology. 2nd ed. Williams & Wilkins Baltimore. 1996: 179-186.

Procopio, G, Verzoni, E, Iacovelli, R, Biasoni, D, Testa, I, Porcu, L, et al. Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies. Br J Cancer. 2012;107(8):1227-32.

Volpe A, Patard JJ. Prognostic factors in renal cell carcinoma. World J Urol. 2010;28:319-27.

Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell. 2007;129:665-79.

Warbrick E. PCNA binding through a conserved motif. BioEssays. 1998;20:195-9.

Gilljam KM, Feyzi E, Aas PA, Sousa MM, Müller R, Vågbø CB, et al. Identification of a novel, widespread, and functionally important PCNA-binding motif. J Cell Biol. 2009;186:645-54.

Mailand N, Gibbs-Seymour I, Bekker-Jensen S. Regulation of PCNA-protein interactions for genome stability. Nature reviews. Molecular Cell Biol. 2013;14:269-82.

Schönenberger F, Deutzmann A, Ferrando-May E, Merhof D. Discrimination of cell cycle phases in PCNA-immunolabeled cells. BMC Bioinform. 2015;16:180.

Wang SC. PCNA: a silent housekeeper or a potential therapeutic target. Trends Pharmacol Sci. 2014;35:178-86.

Schonk DM, Kuijpers HJ, van Drunen E, van Dalen CH, Geurts van Kessel AH, Verheijen R, et al. Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10. Hum Genet. 1989;83:297-9.

Bullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J Cell Physiol. 2006;206:624-35.

Rahmanzadeh R, Hüttmann G, Gerdes J, Scholzen T. Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis. Cell Prolif. 2007;40:422-30.

Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311-22.

Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13-20.

Parker AS, Cerhan JR, Janney CA, Lynch CF, Cantor KP, et al. Smoking cessation and renal cell carcinoma. Ann Epidemiol. 2003;13:245-51.

Puşcaşiu D, Tatu C, Tatu RF, Potencz E, Popescu R, Muntean I, et al. The significance of angiogenesis and tumoral proliferation in renal cell carcinoma. Rom J Morphol Embryol. 2011;52:369-72.

Haitel A, Wiener HG, Migschitz B, Marberger M, Susani M. Proliferating Cell Nuclear Antigen and MIB-1 an alternative to classic prognostic indicators in Renal Cell Carcinomas? Am J Clin Pathol. 1997;107:229-35.

Baretton G, Kublmann B, Krech R, Lohrs U. Intratumoural heterogeneity of nuclear DNA-content and proliferation in clear cell type carcinomas of the kidney. Virchoius Arch B Cell Pathol. 1991;61:57-63.

Droz D, Zacher D, Charbit L, Gogusev J, Chr&tien Y, Lucien I. Expression of the human nephron differentiation molecules in renal cell carcinomas. Am J Pathol. 1990;137:895-905.

Kinouchi T, Saiki S, Naoe T, Uenaka A, Kotake T, Shiku H, et al. Correlation of c-myc expression with nuclear pleomorphism in human renal cell carcinoma. Cancer Res. 1989;49:3627-30.

de Riese WTW, Crabtree WN, Allhoff EP, Werner M, Liedke S, Lenis G, et al. Prognostic significance of Ki-67 immunostaining in non-metastatic renal cell carcinoma. J Cliri Oncol. 1993;ll:1804-8.

Morns GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Cheni. 1989;264:13856-64.