Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press25510.17650/1726-9776-2009-5-3-19-24DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCERДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ МОЧЕПОЛОВОЙ СИСТЕМЫ. Рак мочевого пузыряMOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCERМОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ МАРКЕРЫ КАК ФАКТОРЫ ПРОГНОЗА ТЕЧЕНИЯ ПОВЕРХНОСТНОГО РАКА МОЧЕВОГО ПУЗЫРЯBabayanA. Yu.БабаянА. Ю.
Russian Federation
babayan-a@inbox.ruBashkatovS. V.БашкатовС. В.
Russian Federation
babayan-a@inbox.ruKaryakinO. B.КарякинО. Б.
Russian Federation
babayan-a@inbox.ruTeplovA. A.ТепловА. А.
Russian Federation
babayan-a@inbox.ruGolovashchenkoM. P.ГоловащенкоМ. П.
Russian Federation
babayan-a@inbox.ruShkarupoV. V.ШкарупоВ. В.
Russian Federation
babayan-a@inbox.ruZaletayevD. V.ЗалетаевД. В.
Russian Federation
babayan-a@inbox.ruNemtsovaM. V.НемцоваМ. В.
Russian Federation
babayan-a@inbox.ruResearch Institute of Molecular Medicine, I.M. Sechenov Moscow Medical Academy Medical Genetic Research Center, Russian Academy of Medical Sciences, MoscowНИИ молекулярной медицины ММА им. И.М. Сеченова Медико-генетический научный центр РАМН, МоскваMedical Radiology Research Center, Russian Academy of Medical Sciences, ObninskМРНЦ РАМН, ОбнинскP.A. Herzen Moscow Research Institute of OncologyМНИОИ им. П.А. Герцена300920095319240308201403082014https://oncourology.abvpress.ru/oncur/article/view/255

A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC). However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53), mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood) obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

superficial bladder cancerprognosismolecular genetic markersповерхностный рак мочевого пузыряпрогноз течениямолекулярно-генетические маркеры1. Чиссов В.И., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2006 году (заболеваемость и смертность). М., 2008.Чиссов В.И., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2006 году (заболеваемость и смертность). М., 2008.2. Матвеев Б.П., Фигурин К.Н., Корякин О.Б. Рак мочевого пузыря. М.: Вердана, 2001.Матвеев Б.П., Фигурин К.Н., Корякин О.Б. Рак мочевого пузыря. М.: Вердана, 2001.3. Heney N.M., Ahmed S., Flanagan M.J. et al. Superficial bladder cancer. J Urol 1983;130:1083—6.Heney N.M., Ahmed S., Flanagan M.J. et al. Superficial bladder cancer. J Urol 1983;130:1083—6.4. Babjuk M., Oosterlinck W., Sylvester R. et al. Guidelines on TaT1 (non-muscle invasive) bladder cancer. Arnhem, The Netherlands: European Association of Urology (EAU), 2008.Babjuk M., Oosterlinck W., Sylvester R. et al. Guidelines on TaT1 (non-muscle invasive) bladder cancer. Arnhem, The Netherlands: European Association of Urology (EAU), 2008.5. Sambrook J., Fritsh E.F., Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. N.Y.: Cold Spring Harbor Laboratory Press, 1989.Sambrook J., Fritsh E.F., Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. N.Y.: Cold Spring Harbor Laboratory Press, 1989.6. Землякова В., Жевлова А., Стрельников В. и др. Аномальное метилирование некоторых геновсупрессоров при спорадическом раке молочной железы. Мол Биол 2003;37:696—703.Землякова В., Жевлова А., Стрельников В. и др. Аномальное метилирование некоторых геновсупрессоров при спорадическом раке молочной железы. Мол Биол 2003;37:696—703.7. Кекеева Т., Жевлова А., Подистов Ю. и др. Аномальное метилирование генов супрессоров опухолевого роста и микросателлитная нестабильность в предраковых состояниях шейки матки. Мол Биол 2006;40:224—30.Кекеева Т., Жевлова А., Подистов Ю. и др. Аномальное метилирование генов супрессоров опухолевого роста и микросателлитная нестабильность в предраковых состояниях шейки матки. Мол Биол 2006;40:224—30.8. Van Rhijn B.W., Lurkin I., Radvanyi F. et al. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 2001;61:1265—8.Van Rhijn B.W., Lurkin I., Radvanyi F. et al. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 2001;61:1265—8.9. Knowles M.A. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis 2006;27: 361—73.Knowles M.A. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis 2006;27: 361—73.10. Mhawech-Fauceglia P., Cheney R.T., Schwaller J. Genetic alterations in urothelial bladder carcinoma. Cancer 2006;106(6):1205—16.Mhawech-Fauceglia P., Cheney R.T., Schwaller J. Genetic alterations in urothelial bladder carcinoma. Cancer 2006;106(6):1205—16.11. Akagashi K., Tanda H., Kato S. et al. Recurrence pattern for superficial bladder cancer. Int J Urol 2006;13(6):686—91.Akagashi K., Tanda H., Kato S. et al. Recurrence pattern for superficial bladder cancer. Int J Urol 2006;13(6):686—91.12. Chapman E.J., Harnden P., Chambers P. et al. Comprehensive analysis of CDKN2A status in microdissected urothelial cell carcinoma reveals potential haploinsufficiency, a high frequency of homozygous co-deletion and associations with clinical phenotype. Clin Cancer Res 2005;11(16):5740—7.Chapman E.J., Harnden P., Chambers P. et al. Comprehensive analysis of CDKN2A status in microdissected urothelial cell carcinoma reveals potential haploinsufficiency, a high frequency of homozygous co-deletion and associations with clinical phenotype. Clin Cancer Res 2005;11(16):5740—7.13. Millan-Rodrigez F., Chechile-Toniolo R., Salvador-Bayarri J. Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol (Baltimore) 2000;163:68—7.Millan-Rodrigez F., Chechile-Toniolo R., Salvador-Bayarri J. Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol (Baltimore) 2000;163:68—7.14. Ali-El-Dein B., Sarhan O., Hinev A. et al. Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index. BJU Int 2003;92(4): 393—9.Ali-El-Dein B., Sarhan O., Hinev A. et al. Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index. BJU Int 2003;92(4): 393—9.15. Tada Y., Wada M., Taguchi K. et al. The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Res 2002;62:4048—53.Tada Y., Wada M., Taguchi K. et al. The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Res 2002;62:4048—53.16. Карякин О.Б., Башкатов С.В., Немцова М.В. Клиническое значение молекулярно-генетических изменений в клетках уротелия при раке мочевого пузыря. Онкоурология 2006;3:54—58.Карякин О.Б., Башкатов С.В., Немцова М.В. Клиническое значение молекулярно-генетических изменений в клетках уротелия при раке мочевого пузыря. Онкоурология 2006;3:54—58.17. Sauter G., Mihatstch M.J. et al. Pussycats and baby tigers: non-invasive (pTa) and minimally invasive (pT1) bladder carcinomas are not the same! J Pathology 1998;185:339—41.Sauter G., Mihatstch M.J. et al. Pussycats and baby tigers: non-invasive (pTa) and minimally invasive (pT1) bladder carcinomas are not the same! J Pathology 1998;185:339—41.18. Effert P.J., Seifer P. Invasive potential of «noninvasive» human bladder carcinoma. Am J Clin Pathol 2003;120:188—93.Effert P.J., Seifer P. Invasive potential of «noninvasive» human bladder carcinoma. Am J Clin Pathol 2003;120:188—93.19. Kulkarni G.S., Finelli A., Fleshner N.E. et al. Optimal management of high-risk T1G3 bladder cancer. A decision analysis. PLoS Medicine 2007;4(9):1538—49.Kulkarni G.S., Finelli A., Fleshner N.E. et al. Optimal management of high-risk T1G3 bladder cancer. A decision analysis. PLoS Medicine 2007;4(9):1538—49.20. Thalmann G.N., Markwalder R., Shahin O. et al. Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 2004;172(1):70—5.Thalmann G.N., Markwalder R., Shahin O. et al. Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 2004;172(1):70—5.21. Masood S., Sriprasad S., Palmer J.H., Mufti G.R. T1G3 bladder cancer—indications for early cystectomy. Int Urol Nephrol 2004;36(1):41—4.Masood S., Sriprasad S., Palmer J.H., Mufti G.R. T1G3 bladder cancer—indications for early cystectomy. Int Urol Nephrol 2004;36(1):41—4.22. Manoharan M., Soloway M.S. Optimal management of the T1G3 bladder cancer. Urol Clin North Am 2005;32(2):133—45.Manoharan M., Soloway M.S. Optimal management of the T1G3 bladder cancer. Urol Clin North Am 2005;32(2):133—45.23. Metwalli A.R., Kamat A.M. Controversial issues and optimal management of stage T1G3 bladder cancer. Expert Rev Anticancer Ther 2006;6(8):1283—94.Metwalli A.R., Kamat A.M. Controversial issues and optimal management of stage T1G3 bladder cancer. Expert Rev Anticancer Ther 2006;6(8):1283—94.24. Brandau S., Böhle A. Bladder cancer. I. Molecular and genetic basis of carcinogenesis. Eur Urol 2001;39(5):491—7.Brandau S., Böhle A. Bladder cancer. I. Molecular and genetic basis of carcinogenesis. Eur Urol 2001;39(5):491—7.