Prognostic value of markers of aggressiveness of urinary bladder tumours evaluated by immunohistochemistry
Keywords:
Urinary bladder tumour, immunohistochemistry, prognosis.Abstract
Background: The study of some immunohistochemical markers provides an objective and reproducible prognostic evaluation of urinary bladder tumour.
aims: study the expression of the following immunohistochemical markers in Tumours of the bladder: Proliferating Cell Nuclear Antigen (PCNA), Ki67 antigen (MIB1), the C-erbB2 proto- antigene, the tumor suppressor gene p53, the receptor for epidermal growth factor (EGF-R), the apoptosis suppressor gene bcl2, the carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA).
methods: Study of retrospective series of 30 patients having tumours of the urinary bladder.
results: The expression of PCNA with a cut-off value of 14% is correlated with recurrence (P = 0.010). The expression of PCNA with a cut-off value of 1% is correlated with tumour stage (P = 0.003). The expression of MIB1 with a cut-off value of 47% is correlated with recurrence (P = 0.010). The expression of MIB1 with a cut-off value of 47% is correlated with the tumour progression in stage and\or in grade (P = 0.007). The expression of C-erbB2 with a cutoff value of 28% is correlated in the tumour grade (P = 0.007). The other antibodies didn’t demonstrate a prognostic value.
Conclusion: MIb1 and PCNA being correlated with recurrence, they can be useful with the decision of the rhythm of the endoscopy. The correlation of C-erbB2 with the tumour grade could serve to better graduating bladder tumours.
Downloads
References
Uchida T, Minei S, Gao JP et al. Clinical significance of p53, MDM2 and bcl2 expression in transitional cell carcinoma of the bladder. Oncol Rep 2002; 9: 253-9.
Eble JN, Sauter G, Epstein JI, Sesterhenn TA. World health organisation classification of tumours. Lyon: IARC Press 2004: 89-119.
Maalej M, Mosbah AF. Cancérologie pratique- Cancers de la vessie. Tunis : Centre des publications universitaires 1999: 345- 53.
Molinié V, lonchampt E ,Ouzana D, Lebret T. Tumeurs de vessie et marqueurs moléculaires. Ann Pathol 2003; 23: 306-31.
Burchardt M, Burchardt T, Shabsigh A, et al. Current Concepts in Biomarker Technology for Bladder Cancers. In Clin Chem 2000 ; 46: 595-605.
Gattegno B. Chopin D. Histoire naturelle des tumeurs superficielles de vessie. Prog Urol 2001; 11: 963- 90.
Aveyard P, Adab P, Cheng K K, et al. Does smoking status influence the prognosis of bladder cancer? A systematic review. BJU Int 2002; 90: 228-239.
Ali-El-Dein B, Sarhan O, Hinev A, et al. Superficial bladder tumors: analysis of prognostic factors and construction of a predictive index. BJU Int 2003 ; 92: 393-399.
Sebe P, Lebret T, Molinie V, et al. Tumeurs superficielles de vessie de grade G2 : récidive, progression, pronostic. Prog Urol 2003; 13: 608-612.
Santos LL, Amaro T, Pereira SA, et al. Expression of cell-cycle regulatory proteins and their prognostic value in superficial lowgrade urothelial cell carcinoma of the bladder. Eur J Surg Oncol 2003; 29: 74-80.
Bol MGW, Baak JPA, Van Diermen B, et al. Proliferation markers and DNA content analysis in urinary bladder TaT1 urothelial cell carcinomas: identification of subgroups with low and high stage progression risks. Journal of clinical pathology 2003; 56: 447-52.
RodrÃguez-Alonso A, Pita-Fernández S, González-Carreró J. p53 and ki67 expression as prognostic factors for cancer-related survival in stage T1 transitional cell bladder carcinoma. Eur Urol 2002; 41: 182-9.
Billerey C, Sibony M. Les tumeurs urothéliales dites« superficielles » de la vessie. Quelle classification en 2003 ? Ann Pathol 2003; 23: 21-33.
Rey A, Lara PC, Redondo E, et al. Overexpression of p53 in transitional cell carcinoma of the renal pelvis and ureter. Relation to tumor proliferation and survival. Cancer 1997; 79: 2178-2185.
Skopelitou A, Hadjiyannakis M, Dimopoulos D, et al. p53 and cjun expression in urinary bladder transitional cell carcinoma: correlation with proliferating cell nuclear antigen (PCNA) histological grade and clinical stage. Eur Urol 1997; 31: 464-71.
Chen L, Wang X, Mei H, et al. Apoptosis and expression of PCNA in superficial transitional cell bladder cancer as related to recurrence. Zhonghua Wai Ke Za Zhi 1998; 36: 484-6.
Korkolopoulo P, Christodoulou P, Kapralos P, et al. The role of p53, MDM2 and c-erb B2 oncoproteins, epidermal growth factor receptor and proliferation markers in prognosis of urinary bladder cancer. Pathol Res Pract 1997; 193: 767-75.
Kuezyk MA, Serth J, Bokemeyer C, et al. Value of the proliferation status(PCNA) and p53 immunohistochelistry as a prognostic factor for the clinical course of superficial cancer of the urinary bladder. Urologe A 1995; 34: 146-52.
Hattori K, Uchida K, Akaza H, et al. Proliferating cell nuclear antigen cyclin in human transitional cell carcinoma. Br J Urol 1995; 75: 162-6.
Y Nagase, N Moriyama, S Kurimoto, et al. Histochemical expression of proliferating cell nuclear antigen (PCNA) for preand post chemotherapeutic bladder cancer. Nihon HinyÅkika Gakkai zasshi 1995; 86: 985-90.
Compérat E, Camparo P, Haus R, et al. Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder carcinoma. A tissue microarray study of 158 cases. European Society of Pathology 2006; 448: 319-324.
Matsumoto M, Ohtsuki Y, Ochii K, et al. Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of the urinary bladder, exhibiting no association with low-grade and/or non-invasive lesions. Oncol Rep 2004; 12: 967-71.
Wu TT, Chen JH, Lee YH, Huang JK. The role of BCL-2, p53 and KI-76 index in predicting tumor recurrrence for low grade superficial transitional cell bladder carcima. The Journal of Urology 2000; 163: 758-760.
Fontana D, Bellina M, Gubetta L, et al. Monoclonal antibody Ki- 67 in the study of the proliferative activity of bladder carcinoma. J Urol 1992; 148: 1149-51.
Moch H, Sauter G, Mihatsch MJ, et al. p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer. Hum Pathol 1994; 25: 1346-51.
[26] Lee SE, Chow NH, Chi YC, et al. Expression of c-erbB-2 protein in normal and neoplastic urothelium: lack of adverse prognostic effect in human urinary bladder cancer. Anticancer Res 1994; 14: 1317-24.
Carpenter CD, Ingraham HA, Cochet C, et al. Structural analysis of the transmembrane domain of the epidermal growth factor receptor. J Biol Chem 1991; 266: 5750-5.
Wright C, Thomas D, Mellon K, et al. Expression of retinoblastoma gene product and p53 protein in bladder carcinoma: correlation with Ki67 index. Br J Urol 1995; 75: 173- 9.
Asamoto M, Hasegawa R, Masuko T, et al. Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. Acta Pathol Jpn 1990; 40: 322-6.
Baretton GB, Diebold J, Christoforis G, et al. Apoptosis and immunohistochemical bcl2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance. Cancer 1996; 77: 255-264.
J. Diebold et al., "BCL-2 EXPRESSION, P53 ACCUMULATION, AND APOPTOSIS IN OVARIAN CARCINOMAS", Am J Clin Pathol 1996; 105: 341-349.
Nakopoulou L, Vourlakou C, Zervas A, et al. The prevalence of bcl-2, p53, and Ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates. Hum Pathol 1998; 29: 146-54.
Vollmer RT, Humphrey PA, Swanson PE, et al. Invasion of the bladder by transitional cell carcinoma: its relation to histologic grade and expression of p53, MiB-1, c-erb B-2, epidermal growth factor receptor, and bcl-2. Cancer 1998; 82: 715-723.
Li B, Kanamaru H, Noriki S, et al. Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and carcinoma of the urinary bladder. Urol Res 1998; 26: 235-41.
Nguyen PL, Swanson PE, Jaszcz W, et al. Expression of EGFR in invasive transitional cell carcinoma of the urinary bladder.A multivariate survival analysis. Am J Clin Pathol 1994 ; 101: 166- 76.
Sánchez-Fernández de Sevilla MC, Morell-Quadreny L, Gil- Salom M, et al. Behavior of epithelial differentiation antigens (carcinoembryonic antigen, epithelial membrane antigen, keratin and cytokeratin) in transitional cell carcinomas of the bladder. Urol Int 1992; 48: 14-9.
Jautzke G, Altenaehr E. Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and its correlation with grading and staging on tissue sections of urinary bladder carcinomas. Cancer 1982; 50: 2052-6.