Objective: To conduct a meta-analysis examining p53 expression as a potential risk factor in upper urinary tract urothelial carcinoma (UUT-UC) and to systematically review the available data. Methods: A comprehensive literature review was performed from January 1991 to August 2012, using search engines such as PubMed, EMBASE, Cochrane Library and KoreaMed. All retrieved references were manually reviewed, and two authors independently extracted the data. The quality of case-control and cohort studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) checklists. Heterogeneity among studies was examined using the Q statistics and Higgins' I2 statistic. Results: Of 302 abstracts of original research studies, nine case-control trials fit our criteria for inclusion in the analysis. Of the nine articles included, four scored ‘low' and five scored ‘modest' in the quality assessment performed according to the SIGN checklists. Analysis of the correlation between different factors and p53 expression in UUT-UC showed that pathologic stage (≥pT3 or <pT3) differed significantly between the p53 and non-p53 groups (OR = 2.720, p < 0.001). Statistically significant correlations were also detected between p53 expression and histologic grade (OR = 4.507, p < 0.001) and female gender (OR = 2.724, p < 0.001). Conclusion: The results of our meta-analysis suggest that p53 expression in UUT-UC was correlated with advanced pathologic stage, high histologic grade and female gender.

1.
Bishop JM: Molecular themes in oncogenesis. Cell 1991;64:235-248.
2.
Sidransky D, Messing E: Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors. Urol Clin North Am 1992;19:629-639.
3.
Choi YD, Park JA, Cho NH, Yang WJ, Cho KS, Lee HY, Hong SJ: Expression of p53 and p73 genes in human transitional cell carcinoma of the bladder. Korean J Urol 2004;45:1209-1214.
4.
Lane DP: p53, guardian of the genome. Nature 1992;358:15-16.
5.
Harris CC, Hollstein M: Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318-1327.
6.
Lowe SW, Ruley HE, Jacks T, Housman DE: p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993;74:957-967.
7.
Horowitz JM: Regulation of transcription by the retinoblastoma protein. Genes Chromosomes Cancer 1993;6:124-131.
8.
Kwak DY, Ha JY, Chang HS, Choi MS, Park CH, Kim CI: Clinical implications of the expression of survivin and p53 in superficial transitional cell carcinoma of the bladder. Korean J Urol 2009;50:12-17.
9.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6: e1000097.
10.
Keaney M, Lorimer AR: Auditing the implementation of SIGN (Scottish Intercollegiate Guidelines Network) clinical guidelines. Int J Health Care Qual Assur Inc Leadersh Health Serv 1999;12:314-317.
11.
Flay BR, Biglan A, Boruch RF, Castro FG, Gottfredson D, Kellam S, Moscicki EK, Schinke S, Valentine JC, Ji P: Standards of evidence: criteria for efficacy, effectiveness and dissemination. Prev Sci 2005;6:151-175.
12.
Kumpfer KL, Alvarado R: Family-strengthening approaches for the prevention of youth problem behaviors. Am Psychol 2003;58:457-465.
13.
Broening S, Kumpfer K, Kruse K, Sack PM, Schaunig-Busch I, Ruths S, Moesgen D, Pflug E, Klein M, Thomasius R: Selective prevention programs for children from substance-affected families: a comprehensive systematic review. Subst Abuse Treat Prev Policy 2012;7:23.
14.
Hashimoto H, Sue Y, Saga Y, Tokumitsu M, Yachiku S: 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 2000;7:457-463.
15.
Park S, Hong B, Kim Y, Kim CS, Ahn H: Prognostic factors for survival in the transitional cell carcinoma of the upper urinary tract. Korean J Urol 2003;44:1087-1092.
16.
Shinohara M, Okazawa A, Suzuki M, Itakura H, Munakata A, Kinoshita K: Clinical investigation of renal pelvic and ureteral cancer with special reference to adjuvant chemotherapy. Nihon Hinyokika Gakkai Zasshi 1995;86:1375-1382.
17.
Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG: Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 1998;52:594-601.
18.
Roupret M, Zigeuner R, Palou J, Boehle A, Kaasinen E, Sylvester R, Babjuk M, Oosterlinck W: European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 2011;59:584-594.
19.
Malats N, Bustos A, Nascimento CM, Fernandez F, Rivas M, Puente D, Kogevinas M, Real FX: p53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 2005;6:678-686.
20.
Terrell RB, Cheville JC, See WA, Cohen MB: Histopathological features and p53 nuclear protein staining as predictors of survival and tumor recurrence in patients with transitional cell carcinoma of the renal pelvis. J Urol 1995;154:1342-1347.
21.
Nakanishi K, Kawai T, Torikata C: Immunohistochemical evaluation of p53 oncoprotein in transitional cell carcinoma of the upper urinary tract. Hum Pathol 1996;27:1336-1340.
22.
Jinza S, Takano Y, Iki M, Noguchi S, Masuda M: Prognostic significance of p53 protein overexpression in transitional cell carcinoma of the renal pelvis and ureter. Urol Int 1998;60:147-151.
23.
Bringuier PP, McCredie M, Sauter G, Bilous M, Stewart J, Mihatsch MJ, Kleihues P, Ohgaki H: Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes. Int J Cancer 1998;79:531-536.
24.
Watanabe J, Nishiyama H, Kawanishi H, Ito M, Kamoto T, Ogawa O: Clinical evaluation of serum p53 antibodies in patients with upper urinary tract tumors. J Urol 2005;174: 73-75.
25.
Jeong IG, Kim SH, Jeon HG, Kim BH, Moon KC, Lee SE, Lee E: Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract. Hum Pathol 2009;40:668-677.
26.
Ku JH, Byun SS, Jeong H, Kwak C, Kim HH, Lee SE: The role of p53 on survival of upper urinary tract urothelial carcinoma: a systematic review and meta-analysis. Clin Genitourin Cancer 2013;11:221-228.
27.
Mitchell S, Mayer E, Patel A: Expression of p53 in upper urinary tract urothelial carcinoma. Nat Rev Urol 2011;8:516-522.
28.
Smith ND, Rubenstein JN, Eggener SE, Kozlowski JM: The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol 2003;169:1219-1228.
29.
Furihata M, Yamasaki I, Ohtsuki Y, Sonobe H, Morioka M, Yamamoto A, Terao N, Kuwahara M, Fujisaki N: p53 and human papillomavirus DNA in renal pelvic and ureteral carcinoma including dysplastic lesions. Int J Cancer 1995;64:298-303.
30.
Kang TW, Lee JG, Jung SI, Choi YD, Choi C, Kwon DD, Park K, Ryu SB, Park YI: A study of microsatellite instability of upper urinary tract transitional cell carcinoma. Korean J Urol 2006;47:1269-1277.
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