Ependymal Tumors: Correlation of Proliferative Mib-1 , Tumor Supressor P53 and Anti-Apoptotic Bcl-2 Indices With Histologic Types and Grading
Abstract
Background: The objectives of this study are to investigate both proliferative activity of ependymomas as determined by MIB-1 also known as Ki67 labeling index LI and p53 and bcl-2 proteins by immunohistochemical analysis to assess their expressivity and to correlate findings with ependymoma subtypes and tumor grades. Methods: We investigated routinely formalin-fixed, paraffin-embedded brain and spinal cord biopsy tissues from 33 patients with ependymal neoplasms retrieved from the files of the Neuropathology division, Institute of Neurological Sciences, Marmara University. This study covers 33 tumors with the histological features of 2 subependymomas, 3 myxopapillary ependymomas Grade I , 13 ependymomas Grade II , and 15 anaplastic ependymomas Grade III . Results: Grade I and Grade II ependymomas showed low proliferative activity. P values were significant for atypia p=0.00034, for necrosis p=0.0011, for mitosis p=0.00447, for density p=0.0000. MIB-1 immunexpressivities were seen in 78% of anaplastic ependymomas. Protein expression of bcl-2 was detected in all of ependymoma subtypes and grade, specifically prominent in myxopapillary ependymomas. Seven tumors %21.2 showed nuclear p53 positivity with different percentages with staining of nuclei. Positivity was significant in anaplastic ependymomas %33.4 . We found LI values with significant correlation between supratentorial and infratentorial ependymomas Mann-Whitney-U test, p=0.012 Ki-67 LI values and patients with >18 years old and
Keywords
References
- 1. Duncan JA, Hoffman HJ, Kaye AH, Lows ERJ. Intracranial ependymomas. In: Brain Tumors. Churchill Livingstone, Edinburgh, 1995:493-504
- 2. Zülch KJ. Brain Tumors. In: Their Biology and Pathology. 3rd edition Springer-Verlag, Berlin Heidelberg, 1986:228-247
- 3. Black PM, Loeffler JS. Pathogenic Mechanisms of Nervous System. In Cancer of the Nervous System, Blackwell Science Inc, Edinburgh, 1997:703-743
- 4. Schiffer D. Brain Tumors Biology, Pathology and Clinical References, 2nd edition Springer, Berlin 1997:112-146
- 5. Schiffer D, Chio A, Giordana MT, Migheli A, Palma L, Pollo B, Histologic, prognostic factors in ependymoma. Child Nerv Sys 1991;7:177-182
- 6. Karamitopoulou E, Perentes E, Diamantis I, Maraziotis T, Ki-67 immunoreactivity in human central nervous tumors. a study with MIB-1 monoclonal antibody an archival material. Acta Neuropathol 1994;87:47-54
- 7. Rushing E, Brown D, Hladik C, Risser R, Mickey B, White C. Correlation of bcl-2, p53 and MIB-1 expression with ependymoma grade and subtype. Mod Pathol 1998;5:464-470
- 8. Schröder R, Planer C, Ernetes R. The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 Lİ and MI. Neurosurgery Rev,1993;16:145-150
- 9. Prayson RA. Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. Ann Diag Pathol. 1999;3:11-18
- 10. Suzuki S, Oka H, Kawano N, Tanaka S, Utsuki S, Fujii K. Prognostic value of Ki-67 (MIB-1) and p53 in ependymomas. Brain Tumor Pathol.2001;2:151-154.
- 11. Wolfsberger S, Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K et al. Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol. 2004;7:914-920.
- 12. Suri VS, Tatke M, Singh D, Sharma A. Histological spectrum of ependymomas and correlation of p53 and Ki-67 expression with ependymoma grade and subtype. Indian J Cancer. 2004;2:66-71.
- 13. Feltbower RG, Picton S, Bridges LR, Crooks DA, Glaser AW, McKinney PA. Epidemiology of central nervous system tumors in children and young adults (0-29 years), Yorkshire, United Kingdom. Pediatr Hematol Oncol. 2004;7:647-660.
- 14. Fisher DE. Apoptosis in cancer therapy: crossing the threshold. Cell 1994;78:539-542
- 15. Chamberlain MC. Ependymomas. Curr Neurol Neurosci Rep. 2003;3:193-199.
- 16. Nakasu S, Nakasu L, Nioka H. Bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol.(Berl)1994;88:520-526
- 17. Keer JFR, Winterford CM and Horman BV. Apoptosis. Cancer 1994; 73:2013-2025
- 18. Hallstein M, Sidransky D,Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53
- 19. Ling Ling H, Chang–Feng H, Li-Yu W, Chien-Jen C. p53 gene mutations in brain tumors in Taiwan. Cancer Letters 1994;78:25-32
- 20. Kleihues P, Burger PC, Scheithauer BW. Histological Typing of Tumors of the CNS. WHO International Histological Classification of Tumors 2000. Springer-Verlag Berlin, Heidelberg, New York
- 21. Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC et al. Prognostic factors in intracranial ependymomas in children. Neurosurg. 2000; 4:605-613.
- 22. Korshunov A, Golanov A, Timirgaz V. Immunohistochemical markers for prognosis of ependymal neoplasms. J Neurooncol. 2002;3:255-270.
- 23. Paulino AC, Wen BC, Buatti JM, Hussey DH, Zhen WK, Mayr NA et al. Intracranial ependymomas: an analysis of prognostic factors and patterns of failure. Am J Clin Oncol. 2002;2:117-122.
- 24. Van V-Vincent ML, Pierre-Kahn A, Kalifa C, Sainte-Rose C, Zerah M, Thorne J et al. Ependymoma in childhood: prognostic factors, extent of surgery, and adjuvant therapy. J Neurosurg. 2002;4:827-835.
- 25. Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M et al. Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol 2003;10:980-991
- 26. Jaing TH, Wang HS, Tsay PK, Tseng CK, Jung SM, Lin KL et al. Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas. Neurooncol. 2004;3:255-261.
- 27. Korshunov A, Golanov A, Sycheva R, Timirgaz V. The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 2004;6:1230-1237
- 28. Nazar GB, Hoffman HJ, Becker LE. Infratentorial ependymomas in childhood: prognostic factors and treatment. J Neurosurg. 1990;72:408-417
- 29. Prayson RA, Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunohistochemistry. Mod Pathol Apr 1997;10:4, 304-310
- 30. Saini Y, Niemela A, Kamel D, Herva R, Bloigu R, Paakko P. p53 immunohistochemical positivity as a prognostic marker in intracranial tumors. APMIS 1994;102:786-92
- 31. Korshunov A, Neben K, Wrobel G, Tews B, Benner A, Hahn M et.al. Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am J Pathol. 2003;163:1721-1727.
- 32. The Committee of Brain Tumor Registrory of Japan (1993) Brain Tumor Registory of Japan, Vol 8: National Cancer Center, Tokyo
- 33. Tominigo T, Kayama T, Kumabe T, Sonado Y, Yashimoto T. Anaplastic ependymomas clinical features and tumor suppressor gene p53 analysis. Acta Neurochir. (Wien)1995;135:163-170
Ependimomalarda Antiapoptik BCL-2 Protein ve Tümör Supressör P53 Protein İfadesi ve Proliperatif İndeks Kİ-67 ile Histolojik Tipler ve Derecelerin İlişkisi
Abstract
Amaç: Bu çalışmanın amacı ependimomaların MIB-1 aynı zamanda Ki-67 olarak bilinen işaretleyicisi ile hem proliferatif aktivitesini belirlemek hem de p53 ve bcl-2 proteinlerinin immünohistokimyasal analizi ile ependimoma subtipleri ve tümör derecesi arasında ilişki olup olmadığını değerlendirmektir. Metod: Marmara Üniversitesi Nörolojik Bilimler Enstitüsü Nöropatoloji Bölümünde ependimal tümör olarak kayıtlı 33 hastanın spinal kord ve beyin biyopsi örneklerine ait formalinle fikse parafin blokları tekrar incelendi. Çalışmaya histopatolojik özelliklerini gösteren 2 subependimoma, 3 miksopapiller ependimoma Grade I , 13 ependimoma Grade II , ve 15 anaplastik ependimoma Grade III alındı. Bulgular: Grade I ve Grade II ependimomalar düşük proliferatif aktivite gösterdi. Tüm p değerleri atipide p=0.00034, nekrozda p=0.0011, mitozda p=0.00447 ve dansitede p=0.0000 anlamlı idi. MIB-1 proliferatif indeksi anaplastik ependimomalarda %78 oranında görüldü. Bcl-2 protein ekspresyonu özellikle miksopapiller ependimomalarda belirgin olmak üzere bütün ependimoma subtiplerinde ve gradelerinde tespit edildi. 7 tümör %21.2 farklı boyanma yüzdelerinde nükleer p53 pozitivitesi gösterdi. Pozitivite anaplastik ependimomalarda anlamlı idi %33.4 . Supratentorial ve infratentorial ependimomaların LI değerleri arasında anlamlı ilişki bulundu Mann-Whitney-U testi, p=0.0012 18 yaş altı ve üstü hastaların Ki-67 LI değerleri arasında da aynı testle korelasyon tespit edildi p=0,0018 . Sonuç: Bu veriler yüksek MIB-1 ve p53 değerlerinin yüksek dereceli ependimomalarda belirleyici olabileceğini düşündürdü. Ependimomalarda komplet, uzun süreli klinik takipli çok sayıda hastayı ve bcl-2, p53 ekspresyonu, MIB-1 hücre kinetik çalışmalarını içeren ilave araştırmalara ihtiyaç vardır
Keywords
References
- 1. Duncan JA, Hoffman HJ, Kaye AH, Lows ERJ. Intracranial ependymomas. In: Brain Tumors. Churchill Livingstone, Edinburgh, 1995:493-504
- 2. Zülch KJ. Brain Tumors. In: Their Biology and Pathology. 3rd edition Springer-Verlag, Berlin Heidelberg, 1986:228-247
- 3. Black PM, Loeffler JS. Pathogenic Mechanisms of Nervous System. In Cancer of the Nervous System, Blackwell Science Inc, Edinburgh, 1997:703-743
- 4. Schiffer D. Brain Tumors Biology, Pathology and Clinical References, 2nd edition Springer, Berlin 1997:112-146
- 5. Schiffer D, Chio A, Giordana MT, Migheli A, Palma L, Pollo B, Histologic, prognostic factors in ependymoma. Child Nerv Sys 1991;7:177-182
- 6. Karamitopoulou E, Perentes E, Diamantis I, Maraziotis T, Ki-67 immunoreactivity in human central nervous tumors. a study with MIB-1 monoclonal antibody an archival material. Acta Neuropathol 1994;87:47-54
- 7. Rushing E, Brown D, Hladik C, Risser R, Mickey B, White C. Correlation of bcl-2, p53 and MIB-1 expression with ependymoma grade and subtype. Mod Pathol 1998;5:464-470
- 8. Schröder R, Planer C, Ernetes R. The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 Lİ and MI. Neurosurgery Rev,1993;16:145-150
- 9. Prayson RA. Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. Ann Diag Pathol. 1999;3:11-18
- 10. Suzuki S, Oka H, Kawano N, Tanaka S, Utsuki S, Fujii K. Prognostic value of Ki-67 (MIB-1) and p53 in ependymomas. Brain Tumor Pathol.2001;2:151-154.
- 11. Wolfsberger S, Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K et al. Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol. 2004;7:914-920.
- 12. Suri VS, Tatke M, Singh D, Sharma A. Histological spectrum of ependymomas and correlation of p53 and Ki-67 expression with ependymoma grade and subtype. Indian J Cancer. 2004;2:66-71.
- 13. Feltbower RG, Picton S, Bridges LR, Crooks DA, Glaser AW, McKinney PA. Epidemiology of central nervous system tumors in children and young adults (0-29 years), Yorkshire, United Kingdom. Pediatr Hematol Oncol. 2004;7:647-660.
- 14. Fisher DE. Apoptosis in cancer therapy: crossing the threshold. Cell 1994;78:539-542
- 15. Chamberlain MC. Ependymomas. Curr Neurol Neurosci Rep. 2003;3:193-199.
- 16. Nakasu S, Nakasu L, Nioka H. Bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol.(Berl)1994;88:520-526
- 17. Keer JFR, Winterford CM and Horman BV. Apoptosis. Cancer 1994; 73:2013-2025
- 18. Hallstein M, Sidransky D,Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53
- 19. Ling Ling H, Chang–Feng H, Li-Yu W, Chien-Jen C. p53 gene mutations in brain tumors in Taiwan. Cancer Letters 1994;78:25-32
- 20. Kleihues P, Burger PC, Scheithauer BW. Histological Typing of Tumors of the CNS. WHO International Histological Classification of Tumors 2000. Springer-Verlag Berlin, Heidelberg, New York
- 21. Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC et al. Prognostic factors in intracranial ependymomas in children. Neurosurg. 2000; 4:605-613.
- 22. Korshunov A, Golanov A, Timirgaz V. Immunohistochemical markers for prognosis of ependymal neoplasms. J Neurooncol. 2002;3:255-270.
- 23. Paulino AC, Wen BC, Buatti JM, Hussey DH, Zhen WK, Mayr NA et al. Intracranial ependymomas: an analysis of prognostic factors and patterns of failure. Am J Clin Oncol. 2002;2:117-122.
- 24. Van V-Vincent ML, Pierre-Kahn A, Kalifa C, Sainte-Rose C, Zerah M, Thorne J et al. Ependymoma in childhood: prognostic factors, extent of surgery, and adjuvant therapy. J Neurosurg. 2002;4:827-835.
- 25. Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M et al. Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol 2003;10:980-991
- 26. Jaing TH, Wang HS, Tsay PK, Tseng CK, Jung SM, Lin KL et al. Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas. Neurooncol. 2004;3:255-261.
- 27. Korshunov A, Golanov A, Sycheva R, Timirgaz V. The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 2004;6:1230-1237
- 28. Nazar GB, Hoffman HJ, Becker LE. Infratentorial ependymomas in childhood: prognostic factors and treatment. J Neurosurg. 1990;72:408-417
- 29. Prayson RA, Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunohistochemistry. Mod Pathol Apr 1997;10:4, 304-310
- 30. Saini Y, Niemela A, Kamel D, Herva R, Bloigu R, Paakko P. p53 immunohistochemical positivity as a prognostic marker in intracranial tumors. APMIS 1994;102:786-92
- 31. Korshunov A, Neben K, Wrobel G, Tews B, Benner A, Hahn M et.al. Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am J Pathol. 2003;163:1721-1727.
- 32. The Committee of Brain Tumor Registrory of Japan (1993) Brain Tumor Registory of Japan, Vol 8: National Cancer Center, Tokyo
- 33. Tominigo T, Kayama T, Kumabe T, Sonado Y, Yashimoto T. Anaplastic ependymomas clinical features and tumor suppressor gene p53 analysis. Acta Neurochir. (Wien)1995;135:163-170
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | December 1, 2012 |
| Published in Issue | Year 2012Issue: 4 |