Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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P53 and MDM2 Over-expression and Five-year Survival of Kidney Cancer Patients Undergoing Radical Nephrectomy - Iranian Experience

  • Abolhasani, Maryam (Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences) ;
  • Salarinejad, Sareh (School of Medicine, Iran University of Medical Sciences) ;
  • Asgari, Mojgan (Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences)
  • Published : 2015.07.13
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Abstract

Background: Relatively little is known with certainty about the status and role of p53 or MDM2 in predicting prognosis and survival of renal cell carcinoma. The present study aimed to determine the value of P53 and MDM2 over-expression, alone and simultaneously, to predict five-year survival of patients with kidney cancer in Iran. Materials and Methods: Patients with kidney cancer referred to Hasheminejad Kidney Center between 2007 and 2009, underwent radical nephrectomy and had pathology reports of clear cell, papillary or chromophobe renal cell carcinoma were included in our cohort study. Other histological types of renal cell carcinoma were not included. The patients with missed, incomplete or poor quality paraffin blocks were also excluded. Overall ninety one patients met the inclusion and exclusion criteria. To assess the histopathological features of the tumor, immunohistochemical (IHC) staining of formalin fixed, paraffin-embedded tumor samples were performed. The five-year survival was determined by the patients' medical files and telephone following-up. Results: In total, 1.1% of all samples were revealed to be positive for P53. Also, 20.8% of all samples were revealed to be positive for MDM2.The patients were all followed for 5 years. In this regard, 5-year mortality was 30.5% and thus 5-year survival was 85.3%. According to the Cox proportional hazard analysis, positive P53 marker was only predictor for patients' 5-year survival that the presence of positive p53 increased the risk for long-term mortality up to 2.8 times (HR=2.798, 95%CI: 1.176-6.660, P=0.020). However, the presence of MDM2 could not predict long-term mortality. In this regard, analysis by the ROC curve showed a limited role for predicting long-term survival by confirming P53 positivity (AUC=0.610, 95%CI: 0.471-.750, P=0.106). The best cutoff point for P53 to predict mortality was 0.5 yielding a low sensitivity (32.0%) but a high specificity (97.9%). In similar analysis, measurement of MDM2 positivity could not predict mortality (AUC=0.449, 95%CI: 0.316-.583, P=0.455). Conclusions: The simultaneous presence of both P53 and MDM2 markers in our population is a rare phenomenon and the presence of these markers may not predict long-term survival in patients who undergoing radical nephrectomy.

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References

  1. Akbari ME, Hosseini SJ, Rezaee A, et al (2008). Incidence of genitourinary cancers in the Islamic Republic of Iran: a survey in 2005. Asian Pac J Cancer Prev, 9, 549-52.
  2. Basiri A, Shakhssalim N, Jalaly NY, et al (2014). Difference in the incidences of the most prevalent urologic cancers from 2003 to 2009 in Iran. Asian Pac J Cancer Prev, 15, 1459-63. https://doi.org/10.7314/APJCP.2014.15.3.1459
  3. Chow WH, Gridley G, Fraumeni JF Jr, Jarvholm B (2000). Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med, 343, 1305-11. https://doi.org/10.1056/NEJM200011023431804
  4. Chow WH, Dong LM, Devesa SS (2010). Epidemiology and risk factors for kidney cancer. Nat Rev Urol, 7, 245-57. https://doi.org/10.1038/nrurol.2010.46
  5. Haas NB, Nathanson KL (2014). Hereditary kidney cancer syndromes. Adv Chronic Kidney Dis, 21, 81-90. https://doi.org/10.1053/j.ackd.2013.10.001
  6. 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, 6, 1840-4.
  7. Hashimoto H, Sue Y, Saga Y, Tokumitsu M, Yachiku S (2000). Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter. Int J Urol, 7, 457-63. https://doi.org/10.1046/j.1442-2042.2000.00230.x
  8. Hejnold M, Dyduch G, Bialas M, et al (2014). Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2. Pol J Pathol, 65, 113-9.
  9. Jemal A, Murray T, Ward E, et al (2005). Cancer statistics, 2005.CA Cancer J Clin, 55, 10-30. https://doi.org/10.3322/canjclin.55.1.10
  10. Karami S, Daugherty SE, Schonfeld SJ, et al (2013). Purdue MP Reproductive factors and kidney cancer risk in 2 US cohort studies, 1993-2010. Am J Epidemiol, 177, 1368-77. https://doi.org/10.1093/aje/kws406
  11. Kim HL, Seligson D, Liu X, et al (2004). Using protein expressions to predict survival in clear cell renal carcinoma. Clin Cancer Res, 10, 5464-71. https://doi.org/10.1158/1078-0432.CCR-04-0488
  12. Ljungberg B, Bozoky B, Kovacs G, et al (2001). p53 expression in correlation to clinical outcome in patients with renal cell carcinoma. Scand J Urol Nephrol, 35, 15-20. https://doi.org/10.1080/00365590151030705
  13. Moch H (2013). An overview of renal cell cancer: pathology and genetics. Semin Cancer Bio, 23, 3-9. https://doi.org/10.1016/j.semcancer.2012.06.006
  14. Moore LE, Wilson RT, Campleman SL (2005). Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest. 23, 240-55. https://doi.org/10.1081/CNV-200055962
  15. Noon AP, Pola.ski R, El-Fert AY, et al (2012). Combined p53 and MDM2 biomarker analysis shows a unique pattern of expression associated with poor prognosis in patients with renal cell carcinoma undergoing radical nephrectomy. BJU Int, 109, 1250-7. https://doi.org/10.1111/j.1464-410X.2011.10433.x
  16. Olumi AF, Weidner N, Presti JC (2001). p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma. Urol Oncol, 6, 63-67. https://doi.org/10.1016/S1078-1439(00)00109-5
  17. Polanski BR (2010). Use of MDM2 to link survival and invasiveness in renal cell carcinoma and as a novel drug target for therapy. 2010 Genitourinary Cancers Symposium, Abstract No 320.
  18. Sanfilippo KM, McTigue KM, Fidler CJ, et al (2014).Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women. Hypertension, 63, 934-41. https://doi.org/10.1161/HYPERTENSIONAHA.113.02953
  19. Shuch B, Vourganti S, Ricketts CJ, et al (2014). Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J ClinOncol, 32, 431-7. https://doi.org/10.1200/JCO.2013.50.8192
  20. Uchida T, Gao JP, Wang C, et al (2002). Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma. Urology, 59, 615-20. https://doi.org/10.1016/S0090-4295(01)01601-6
  21. Uzunlar AK, Sahin H, Yilmaz F, Ozekinci S (2005). Expression of p53 oncoprotein and bcl-2 in renal cell carcinoma. Saudi Med J, 26, 37-41.
  22. Washio M, Mori M, Mikami K, et al (2014). Risk factors for renal cell carcinoma in a Japanese population. Asian Pac J Cancer Prev, 15, 9065-70. https://doi.org/10.7314/APJCP.2014.15.21.9065
  23. Yap NY, Ng KL, Ong TA, et al (2013), Clinical prognostic factors and survival outcome in renal cell carcinoma patients--a malaysian single centre perspective. Asian Pac J Cancer Prev, 14, 7497-500. https://doi.org/10.7314/APJCP.2013.14.12.7497
  24. Zigeuner R, Ratschek M, Rehak P, Schips L, Langner C (2004). Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue. Urology, 63, 651-5. https://doi.org/10.1016/j.urology.2003.11.011

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