vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestim-304Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ГИСТОЛОГИЧЕСКИХ И МОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИХ КРИТЕРИЕВ ПРИ ПЕРЕХОДНО-КЛЕТОЧНОМ НЕИНВАЗИВНОМ РАКЕ МОЧЕВОГО ПУЗЫРЯPROGNOSTIC VALUE OF HISTOLOGICAL AND MOLECULAR-BIOLOGICAL CHARACTERISTICS IN TRANSITIONAL-CELL NON-MUSCLE INVASIVE BLADDER CANCERНабебинаТ. И.NabebinaT.nabebina.t@yandex.byРолевичА. И.RolevichA.alexander.rolevich@gmail.comДубровскийА. Ч.DubrouskiA.dubr@omr.med.byПоляковС. Л.PolyakovS.s.polyakov@yahoo.comКрасныйС. А.KrasnyS.sergeykrasny@tut.byРеспубликанский научно-практический центр онкологии и медицинской радиологии им. Н. Н. АлександроваN. N. Alexandrov National Research Cancer Centre201604082016025060Copyright © Набебина Т.И., Ролевич А.И., Дубровский А.Ч., Поляков С.Л., Красный С.А., 20162016Набебина Т.И., Ролевич А.И., Дубровский А.Ч., Поляков С.Л., Красный С.А.Nabebina T., Rolevich A., Dubrouski A., Polyakov S., Krasny S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/304

Оценено прогностическое значение стандартных гистологических и молекулярно-биологических признаков при переходно-клеточном раке мочевого пузыря без мышечной инвазии в группе пациентов с высоким риском прогрессирования по критериям EORTC; определена группа лиц, которым показано выполнение ранней цистэктомии. Ретроспективно изучены доступные данные о характере течения заболевания и последующем наблюдении 179 пациентов, пролеченных в 2004–2007 гг. посредством выполнения трансуретральной резекции (с/без последующей внутрипузырной терапии). С помощью световой микроскопии препаратов определены стандартные гистологические характеристики переходно-клеточного рака, в опухолевом материале с помощью иммуногистохимических методов установлены уровни экспрессии Ki67, р53, р63, CK 20, СK 18, CK 10/13 и CK 5/6. Проведена статистическая обработка результатов, изучена корреляция вышеуказанных параметров с показателем выживаемости без прогрессирования (PFS, определяемая как развитие инвазии мышечного слоя, метастазов или смерти от рака). Установлено, что отношение рисков прогрессирования заболевания в течение 5 лет у пациентов, страдающих переходно-клеточным раком, с наличием в опухоли позитивной ядерной реакции с антителами к белку р53 в 50 % и более клеток опухоли и/или позитивной цитоплазматической реакции с антителами к СК 5/6 в 50 % и более клеток опухоли, по сравнению с пациентами, не имеющими указанных факторов негативного прогноза, составляет 3,97 (95 %-ный доверительный интервал 2,25–7,01) (р < 0,001).

The prediction of disease progression in patients with high-risk transitional-cell non-muscle invasive bladder cancer (NMIBC) can help in the decision-making for patients eligible to early cystectomy. In this study we evaluated the association of different immunohistochemical tissue markers in patients with NMIBC at a high risk of disease progression. 179 patients with NMIBC that underwent complete TUR ± intravesical therapy between 2004 and 2007 and available follow-up were selected. Microscopic slides were reviewed: tumour stage, grade (WHO 1973 and 2004), the presence of carcinoma in situ and lymphovascular invasion was determined. Additionally, the expression of Ki67, р53, р63, CK 20, СK 18, CK 10/13 and CK 5/6 was determined after immunohistochemical staining of paraffin embedded tissue samples. The pathology results were correlated with the progression-free survival (PFS defined as the development of the muscle invasive disease, metastases or the death from cancer). 5-year PFS in patients with positive nuclear staining (≥50 %) with р53 antibodies and/or positive cytoplasm staining with CK 5/6 (≥50 %) was 55 % (95 % CI 39–70) compared to 84 % (95 % CI 77–90) in patients without the expression of these markers (HR 4.0, 95 % CI 2.2–7.0 (p < 0.001).

рак мочевого пузыря без мышечной инвазиивероятность прогрессированияпрогностическое значение стандартных гистологических и молекулярно-биологических признаковгиперэкспрессиия р53 и СК 5/6non-muscle invasive bladder cancerprogression probabilityprognostic value of histological and molecular characteristicsр53 and CK 5/6 over expressionReferencesСтатистика онкологических заболеваний / А. Е. Океанов [и др.]; под ред. О. Г. Суконко. – Минск: РНПЦ ОМР им. Н. Н. Александрова, 2014. – С. 171–177.Статистика онкологических заболеваний / А. Е. Океанов [и др.]; под ред. О. Г. Суконко. – Минск: РНПЦ ОМР им. Н. Н. Александрова, 2014. – С. 171–177.Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy / Bas W. G. van Rhijn [et al.] // Eur. Urol. – 2009. – Vol. 56, N 3. – P. 430–442.Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy / Bas W. G. van Rhijn [et al.] // Eur. Urol. – 2009. – Vol. 56, N 3. – P. 430–442.Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials / Richard J. Sylvester [et al.] // Eur. Urol. – 2006. – Vol. 49, N 3. – P. 466–477.Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials / Richard J. Sylvester [et al.] // Eur. Urol. – 2006. – Vol. 49, N 3. – P. 466–477.The health economics of bladder cancer: a comprehensive review of the published literature / M. F. Botteman [et al.] // Pharmacoeconomics. – 2003. – Vol. 21, N 18. – P. 1315–1330.The health economics of bladder cancer: a comprehensive review of the published literature / M. F. Botteman [et al.] // Pharmacoeconomics. – 2003. – Vol. 21, N 18. – P. 1315–1330.Economic aspects of bladder cancer: what are the benefits and costs? / K. D. Sievert [et al.] // World J. Urol. – 2009. – Vol. 27, N 3. – P. 295–300.Economic aspects of bladder cancer: what are the benefits and costs? / K. D. Sievert [et al.] // World J. Urol. – 2009. – Vol. 27, N 3. – P. 295–300.Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review / S. van den Bosch [et al.] // Eur. Urol. – 2011. – Vol. 60, N 3. – P. 493–500.Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review / S. van den Bosch [et al.] // Eur. Urol. – 2011. – Vol. 60, N 3. – P. 493–500.High-risk nonmuscle invasive bladder cancer / A. Orsola [et al.] // Hematol. Oncol. Clin. North Am. – 2015. – Vol. 29, N 2. – P. 227–236.High-risk nonmuscle invasive bladder cancer / A. Orsola [et al.] // Hematol. Oncol. Clin. North Am. – 2015. – Vol. 29, N 2. – P. 227–236.Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? / H. W. Herr [et al.] //J. Urol. – 2001. – Vol. 166, N 4. – P. 1296–1299.Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? / H. W. Herr [et al.] //J. Urol. – 2001. – Vol. 166, N 4. – P. 1296–1299.Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette- Guérin: multivariate analysis of data from four randomized CUETO trials / J. Fernandez-Gomez [et al.] // Eur. Urol. – 2008. – Vol. 53, N 5. – P. 992–1002.Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette- Guérin: multivariate analysis of data from four randomized CUETO trials / J. Fernandez-Gomez [et al.] // Eur. Urol. – 2008. – Vol. 53, N 5. – P. 992–1002.Mostofi, F. K. Histological typing of urinary bladder tumours. International Histological Classification of Tumors /F. K. Mostofi, L. H. Sobin, H. Torloni. – Geneva: World Health Organization, 1973. – Vol. 10.Mostofi, F. K. Histological typing of urinary bladder tumours. International Histological Classification of Tumors /F. K. Mostofi, L. H. Sobin, H. Torloni. – Geneva: World Health Organization, 1973. – Vol. 10.Eble, J. N. World Health Organization classification of tumours: pathology and genetics of tumours of the urinarysystem and male genital organs / J. N. Eble. – Lyon: IARCPress, 2004.Eble, J. N. World Health Organization classification of tumours: pathology and genetics of tumours of the urinarysystem and male genital organs / J. N. Eble. – Lyon: IARCPress, 2004.Diagnostic algorithm for papillary urothelial tumors in the urinary bladder / Jung-Weon Shim [et al.] // Virchows Arch. – 2008. – Vol. 452. – P. 353–362.Diagnostic algorithm for papillary urothelial tumors in the urinary bladder / Jung-Weon Shim [et al.] // Virchows Arch. – 2008. – Vol. 452. – P. 353–362.Histologic grading of urothelial carcinoma: a reappraisal / L. Cheng [et al.] // Human Pathol. – 2012. – Vol. 43. –P. 2097–2108.Histologic grading of urothelial carcinoma: a reappraisal / L. Cheng [et al.] // Human Pathol. – 2012. – Vol. 43. –P. 2097–2108.An Approach to the Diagnosis of Flat Intraepithelial Lesions of the Urinary Bladder Using the World Health Organization International Society of Urological Pathology Consensus Classification System / Mahul B. Amin [et al.] // Advances in Anatomic Pathol. – 2002. – Vol. 9. – P. 222–232.An Approach to the Diagnosis of Flat Intraepithelial Lesions of the Urinary Bladder Using the World Health Organization International Society of Urological Pathology Consensus Classification System / Mahul B. Amin [et al.] // Advances in Anatomic Pathol. – 2002. – Vol. 9. – P. 222–232.A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage / Bas W. G. van Rhijn [et al.] // Eur. Urol. – 2012. – Vol. 61, N 6. – P. 378–384.A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage / Bas W. G. van Rhijn [et al.] // Eur. Urol. – 2012. – Vol. 61, N 6. – P. 378–384.Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients / P. Gontero [et al.] // Eur. Urol. – 2015. – Vol. 67, N 1. – P. 74–82.Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients / P. Gontero [et al.] // Eur. Urol. – 2015. – Vol. 67, N 1. – P. 74–82.Improving selection criteria for early cystectomy in high-grade T1 bladder cancer: a meta-analysis of 15,215 patients / W. Martin-Doyle [et al.] // J. Clin. Oncol. – 2015. – Vol. 33, N 6. – P. 643–650.Improving selection criteria for early cystectomy in high-grade T1 bladder cancer: a meta-analysis of 15,215 patients / W. Martin-Doyle [et al.] // J. Clin. Oncol. – 2015. – Vol. 33, N 6. – P. 643–650.Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy? / R. Segal [et al.] // BJU Int. – 2012. – Vol. 109, N 7. – P. 1026–1030.Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy? / R. Segal [et al.] // BJU Int. – 2012. – Vol. 109, N 7. – P. 1026–1030.Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients / A. Orsola [et al.] // Br. J. Cancer. – 2015. – Vol. 112, N 3. – P. 468–474.Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients / A. Orsola [et al.] // Br. J. Cancer. – 2015. – Vol. 112, N 3. – P. 468–474.The p53 pathway and outcome among patients with T1G3 bladder tumors / E. Lopez-Knowles [et al.] // Clin. Cancer Res. – 2006. – Vol. 12, N 15. – P. 6029–6036.The p53 pathway and outcome among patients with T1G3 bladder tumors / E. Lopez-Knowles [et al.] // Clin. Cancer Res. – 2006. – Vol. 12, N 15. – P. 6029–6036.Prognostic value of p53 for high risk superficial bladder cancer with long-term follow up / P. M. Moonen [et al.] // J. Urol. – 2007. – Vol. 177, N 1. – P. 80–83.Prognostic value of p53 for high risk superficial bladder cancer with long-term follow up / P. M. Moonen [et al.] // J. Urol. – 2007. – Vol. 177, N 1. – P. 80–83.P53 as a prognostic marker for bladder cancer: a meta-analysis and review / N. Malats [et al.] // Lancet Oncol. – 2005. – Vol. 6, N 9. – P. 678–686.P53 as a prognostic marker for bladder cancer: a meta-analysis and review / N. Malats [et al.] // Lancet Oncol. – 2005. – Vol. 6, N 9. – P. 678–686.P53 immunohistochemistry in bladder cancer: a new approach to an old question / P. J. Goebell [et al.] // Urol. Oncol. – 2010. – Vol. 28, N 4. – P. 377–388.P53 immunohistochemistry in bladder cancer: a new approach to an old question / P. J. Goebell [et al.] // Urol. Oncol. – 2010. – Vol. 28, N 4. – P. 377–388.Biomarkers for bladder cancer management: present and future // Fei Ye [et al.] // Am. J. Clin. Exp. Urol. – 2014. – Vol. 2, N 1. – P. 1–14.Biomarkers for bladder cancer management: present and future // Fei Ye [et al.] // Am. J. Clin. Exp. Urol. – 2014. – Vol. 2, N 1. – P. 1–14.A molecular taxonomy for urothelial carcinoma / G. Sjodahl [et al.] // Clin. Cancer Res. – 2012. – Vol. 18, N 12. – P. 3377–3386.A molecular taxonomy for urothelial carcinoma / G. Sjodahl [et al.] // Clin. Cancer Res. – 2012. – Vol. 18, N 12. – P. 3377–3386.A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma // O. Patschan [et al.] // Eur. Urol. – 2015. – Vol. 68, N 5. – P. 833–834.A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma // O. Patschan [et al.] // Eur. Urol. – 2015. – Vol. 68, N 5. – P. 833–834.Three differentiation states risk-stratify bladder cancer into distinct subtypes / J. P. Volkmer [et al.] // Proc. Natl. Acad. Sci. USA. – 2012. – Vol. 109, N 6. – P. 2078–2083.Three differentiation states risk-stratify bladder cancer into distinct subtypes / J. P. Volkmer [et al.] // Proc. Natl. Acad. Sci. USA. – 2012. – Vol. 109, N 6. – P. 2078–2083.Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy / W. Choi [et al.] // Сancer Cell. – 2014. – Vol. 25, N 2. – P. 152–165.Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy / W. Choi [et al.] // Сancer Cell. – 2014. – Vol. 25, N 2. – P. 152–165.

The authors declare that there are no conflicts of interest present.