Tumor Markers of Bladder Cancer: the Schistosomal Bladder Tumors Versus Non-schistosomal Bladder Tumors

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2009 Feb 27

PMID 19243595

Citations 25

Authors

Ahmed S Abdulamir

Rand R Hafidh

Haider S Kadhim

Fatimah Abubakar

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT).

Methods: This study explored the role of p53, p16, bcl-2, ki-67, c-myc, Rb and EGFR, by using Immunohistochemistry assay, in 45 SBT and 39 NSBT patients in comparison with 16 schistosomal chronic cystitis (SC), 28 non-schistosomal chronic cystitis (NSC), and 20 normal control (CTL) subjects. The studied markers in SBT and NSBT were correlated with different clinicopathological criteria namely, tumor histopathology, grading, invasiveness, stage, and presentation of the disease.

Results: SBT was associated with high grade invasive squamous cell carcinoma (SCC) while NSBT was associated with lower grade less invasive transitional cell carcinoma (TCC). The expression of p53, bcl-2, c-myc, and EGFR was higher in SBT than in NSBT while Rb was higher in NSBT than in SBT. However, p16 and ki-67 were not different between SBT and NSBT. The profile of molecular markers in SC was similar to NSC except for EGFR which was higher in SC than in NSC. Both SC and NSC showed higher level of p53, bcl-2, ki-67, and EGFR than in CTL group while p16, Rb, and c-myc were not different. p53 was associated with high grade SCC in both SBT and NSBT. Bcl-2 was associated with high grade invasive tumors in SBT and NSBT. P16 was associated with low grade, late stage, and recurrent SBT and high grade, invasive, late stage, and recurrent NSBT. Rb was associated with SCC in SBT, invasive tumors in NSBT, and late stage and recurrent presentation in both SBT and NSBT. C-myc was associated with high grade, invasive, and late stage SBT and SCC, high grade, invasive, and late stage NSBT. EGFR was associated with invasive SCC in SBT and invasive, high grade, and late stage TCC in NSBT. ki-67 was associated with invasive SBT and high grade late stage NSBT.

Conclusion: SBT and NSBT showed distinct molecular profile of tumor development and progression which can be taken into consideration in fine adjusting the anti-cancer therapy for SBT and NSBT.

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Urogenital Schistosomiasis-History, Pathogenesis, and Bladder Cancer.

Santos L, Santos J, Gouveia M, Bernardo C, Lopes C, Rinaldi G J Clin Med. 2021; 10(2).

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References

Nakopoulou L, Vourlakou C, Zervas A, Tzonou A, Gakiopoulou H, Dimopoulos M . The prevalence of bcl-2, p53, and Ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates. Hum Pathol. 1998; 29(2):146-54. DOI: 10.1016/s0046-8177(98)90225-8. View

Sandberg A, Berger C . Review of chromosome studies in urological tumors. II. Cytogenetics and molecular genetics of bladder cancer. J Urol. 1994; 151(3):545-60. DOI: 10.1016/s0022-5347(17)35014-0. View

El-Hawey A, Amr M, Abdel-Rahman A, Agina A, Abdel-Hafez M, Waheeb A . The epidemiology of schistosomiasis in Egypt: Gharbia Governorate. Am J Trop Med Hyg. 2000; 62(2 Suppl):42-8. DOI: 10.4269/ajtmh.2000.62.42. View

Pich A, Margaria E, Chiusa L, Bortolin P, Palestro G . Relationship between AgNORs, MIB-1 and oncogene expression in male breast carcinoma and papillary superficial bladder neoplasm. Oncol Rep. 2003; 10(5):1329-35. View

del Senno L, Maestri I, Piva R, Hanau S, Reggiani A, Romano A . Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades. J Urol. 1989; 142(1):146-9. DOI: 10.1016/s0022-5347(17)38700-1. View

Brunner A, Verdorfer I, Prelog M, Mayerl C, Mikuz G, Tzankov A . Large-scale analysis of cell cycle regulators in urothelial bladder cancer identifies p16 and p27 as potentially useful prognostic markers. Pathobiology. 2008; 75(1):25-33. DOI: 10.1159/000113792. View

El A Helal T, Fadel M, El-Sayed N . Human papilloma virus and p53 expression in bladder cancer in Egypt: relationship to schistosomiasis and clinicopathologic factors. Pathol Oncol Res. 2006; 12(3):173-8. DOI: 10.1007/BF02893365. View

Masliukova E, Pozharisskii K, Karelin M, Startsev V, Ten V . [Role of Ki-67, mutated gene-suppressor p53 and HER-2neu oncoprotein in the prognosis for the clinical course of bladder cancer]. Vopr Onkol. 2007; 52(6):643-8. View

Tawfik H . Carcinoma of the urinary bladder associated with schistosomiasis in Egypt: the possible causal relationship. Princess Takamatsu Symp. 1987; 18:197-209. View

10.

Badr K, Nolen J, Derose P, Cohen C . Muscle invasive schistosomal squamous cell carcinoma of the urinary bladder: frequency and prognostic significance of p53, BCL-2, HER2/neu, and proliferation (MIB-1). Hum Pathol. 2004; 35(2):184-9. DOI: 10.1016/j.humpath.2003.10.006. View

11.

Williams S, Buscarini M, Stein J . Molecular markers for diagnosis, staging, and prognosis of bladder cancer. Oncology (Williston Park). 2002; 15(11):1461-70, 1473-4, 1476; discussion 1476-84. View

12.

Colquhoun A, Mchugh L, Tulchinsky E, Kriajevska M, Mellon J . Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo. J Radiat Res. 2007; 48(5):351-60. DOI: 10.1269/jrr.07014. View

13.

Mitra A, Birkhahn M, Cote R . p53 and retinoblastoma pathways in bladder cancer. World J Urol. 2007; 25(6):563-71. DOI: 10.1007/s00345-007-0197-0. View

14.

Cho H, Kim J, Kim K, Yoon H, Cho M, Park Y . Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells. Cancer Lett. 2005; 237(1):56-66. DOI: 10.1016/j.canlet.2005.05.039. View

15.

Haitel A, Posch B, El-Baz M, Mokhtar A, Susani M, Ghoneim M . Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2. J Urol. 2001; 165(5):1481-7. View

16.

Lindboe C, Torp S . Comparison of Ki-67 equivalent antibodies. J Clin Pathol. 2002; 55(6):467-71. PMC: 1769671. DOI: 10.1136/jcp.55.6.467. View

17.

Lipponen P . Expression of c-myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer. J Pathol. 1995; 175(2):203-10. DOI: 10.1002/path.1711750208. View

18.

Mostafa M, Sheweita S, OConnor P . Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev. 1999; 12(1):97-111. PMC: 88908. DOI: 10.1128/CMR.12.1.97. View

19.

Atug F, Turkeri L, Ozyurek M, Akdas A . Bcl-2 and p53 overexpression as associated risk factors in transitional cell carcinoma of the bladder. Int Urol Nephrol. 1998; 30(4):455-61. DOI: 10.1007/BF02550226. View

20.

Eissa S, Ali-Labib R, Khalifa A . Deletion of p16 and p15 genes In schistosomiasis-associated bladder cancer (SABC). Clin Chim Acta. 2000; 300(1-2):159-69. DOI: 10.1016/s0009-8981(00)00317-x. View