Caner ÖZBEY, Elif İnanç GÜRER, Güzide Ayşe OCAK

Glial Tümörlerde DNA Piloidi ve Ki-67 Proliferatif İndeksi ile Tümör Derecesi Arasındaki İlişki

Amaç: Glial tümörler en sık görülen primer beyin tümörleridir.Tümör hücrelerinde DNA piloidi ve proliferasyon indeksi belirlenmesi, birçok neoplazide olduğu gibi glial tümörlerde de prognoz ile yakından ilişkilidir. Bu çalışmanın amacı glial tümörlerde DNA piloidi ve Ki-67 proliferatif indeksi tayini ile tümör dereceleri arasındaki ilişkiyi incelemektir. Gereç ve Yöntemler: Bu çalışmaya Ekim 2003 ile Haziran 2005 tarihleri arasında Akdeniz Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı tarafından incelenen 30 glial tümör olgusu alındı. DNA piloidi belirlenmesi için ameliyat sırasında tümör dokusundan hazırlanan imprint preparat, histokimyasal Feulgen boyama tekniğiyle boyanıp, Autocyte Quic® DNA programı kullanılarak incelendi. Ki-67 proliferatif indeksini belirlemek için parafin bloktan alınan kesitlere immünohistokimyasal Ki-67 boyası uygulandı. Işık mikroskopide 400x büyütmede toplam 1000 tümör hücresinde pozitif nükleer boyanan hücreler sayıldı ve yüzdeleri alındı. Olgularda derece belirlemek için Dünya Sağlık Örgütü dereceleme sistemi kullanıldı.Bulgular: Tümör derecesi ile DNA indeksi DI ve Ki-67 proliferatif indeksi arasında anlamlı ilişki bulundu. Yüksek dereceli tümörlerde bu iki parametrenin de düşük dereceli tümörlere göre daha yüksek olduğu bulundu. Ki-67 proliferatif indeksi ile DI arasında da anlamlı ilşki bulundu. Yüksek Ki-67 değerleri yüksek DI değerleri ile ilişkiliydi.Sonuç: Glial tümörlerin DNA piloidisi ve Ki-67 proliferatif indeksi tümör derecesi hakkında güvenilir bilgi vermektedir. DNA piloidisinin, Ki-67 proliferatif indeks ve histopatolojik tanı/derece ile beraber daha objektif prognostik veriler elde edilmesine olanak sağlayacağını düşünmekteyiz

Anahtar Kelimeler:

DNA piloidi, Glial tümörler, Ki-67

Relationship between DNA Ploidy, Ki-67 Proliferation Index and Tumor Grade in Glial Tumors

Objective: Glial tumors are the most common primary brain neoplasms. As in many tumors, evaluation of DNA ploidy and the proliferation index have prognostic relevance in glial tumors. In this study, we aimed to evaluate the DNA ploidy and Ki-67 proliferation index values of 30 glial tumors and their relationship with the tumor grade.Material and Methods: Thirty glial tumor cases were investigated in this study between October 2003 and June 2005 at the Akdeniz University Faculty of Medicine Pathology Department. During surgery, we prepared touch preparations of tumors and then we stained them with the histochemical Feulgen staining technique. We examined Feulgen stained preparations using the Autocyte Quic® DNA program to determine the DNA ploidy. For the proliferation index, Ki-67 immunohistochemical staining was performed on the sections prepared from paraffin embedded tissue blocks. Positive nuclear stained cells were counted in a total of 1000 tumor cells at 400x magnification using a light microscope and the percentages were calculated. The World Health Organization grading system was used to grade the tumors.Results: We established that tumor grade has a good correlation with DNA index DI and Ki-67 values. These two parameters had higher values in high grade tumors than low grade ones. There was also a significant correlation between the Ki-67 proliferation index and DI. High Ki-67 values were associated with high DI values. Conclusion: In glial tumors, DNA ploidy and Ki-67 proliferative index provide reliable information about tumor grade. In addition to tumor grade, determining DNA ploidy and Ki-67 proliferation index in glial tumors help us predict the prognosis more objectively in glial tumors

Keywords:

DNA ploidy, Glial tumors, Ki-67,

PDF

___

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol 2016; 131(6):803-20.
Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. Journal of Neuropathology and Experimental Neurology 2005; 64(6):479-89.
Bağdatoğlu C, Silav G, Kanık A, Dolgun H, Bademci G, Deda H. The importance of flow cytometric dna analysis in glial tumors. Turkish Neurosurgery 2001; 11:18-25.
Coons SW, Davis JR, Way DL. Correlation of DNA content and histology in prognosis of astrocytomas. Am J Clin Pathol 1988; 90(3):289-93.
Zaprianov Z, Christov K. Histological grading, DNA content, cell proliferation and survival of patients with astroglial tumors. Cytometry 1988; 9(4):380-6.
Reis A, Baykal S, Kuzeyli K, Tekelioğlu Y, Özoran Y, Ovalı E, Çobanoğlu Ü, Çakır E. Astrositomlarda akım sitometrik inceleme ve p53 protein ile EGFR immünreaktivitesi. Türk Nöroşirürji Dergisi 1999; 9(3):1-6.
Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M, Kodet R. Pediatric intracranial ependymomas: Prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Patho 2003; 16(10):980-91.
Mathew P, Look T, Luo X, Ashmun R, Nash M, Gajjar A, Walter A, Kun L, Heideman RL. DNA index of glial tumors in children: Correlation with tumor grade and prognosis. Cancer 1998; 78(4), 881-6.
El-Rayes BF, Norton CS, Sakr W, Maciorowski Z, Smith D, Pietraszkiewicz H, Del Mar Alonso M, Ensley JF. DNA content parameters as prognostic indicators in human astrocytomas; Journal of Neuro-Oncology 2005; 71(2): 85-9.
Gasińska A, Krzyszk wski T, Niemiec J, Adamczyk A, Skołyszewski J. Prognostic significance of DNA ploidy and proliferation rate in human astrocytic gliomas. Folia Histochem Cytobiol 2000; 38(4):175-80.
Budak Y, Kurtkaya Ö, Yanıkkaya Demirel G, Baloğlu H, Işıtmangil G. Diffüz astrositoma olgularında DNA içerik tayini. İstanbul Üniversitesi İstanbul Tıp Fakültesi Dergisi 2004; 67(2):83-91.
Darzynkiewicz Z, Crissman H, Jacobberger JW. Cytometry of the cell cycle: Cycling through history. Cytometry A 2004; 58(1):21-32.
Giaretti W. Flow cytometry and applications in oncology. Clin Pathol 1997;50:275-7.
Meijer GA, Beliën JA, van Diest PJ, Baak JP. Image analysis in clinical pathology. Clin Pathol 1997; 50:365- 70.
Suzuki S, Oka H, Kawano N, Tanaka S, Utsuki S, Fujii K. Prognostic value of Ki-67 (MIB-1) and p53 in eependymomas. Brain Tumor Pathol 2001; 18:151-4.
Bennetto L, Foreman N, Harding B, Hayward R, Ironside J, Love S, Ellison D. Ki-67 immunolebeling index is a prognostic indicator in childhood posterior fossa ependymomas. Neuropathol Appl Neurobiol 1998; 24:434-40.
Figarella-Branger D, Civatte M, Boovier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, Lena G, Choux M, Pellissier JF. Prognostic factors in intracranial ependymomas in children. Journal of Neurosurgery 2000; 93:605-13.
Ho DM, Hsu CY, Wong TT, Chian H. A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma. J Neurooncol 2001; 54:77-85.
Schroder R, Ploner C, Ernestus RI. The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 labeling index and mitotic index. Neurosurg Rev 1993; 16:145-50.
Ritter AM, Hess KR, McLendon RE, Langford LA. Ependymomas. MIB-1 proliferation index and survival. J Neurooncol 1998; 40:51-7.
Rushing EJ, Brown DF, Hladik CL, Risser RC, Mickey BE, White CL. Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype. Mod Pathol 1998; 11:464-70.
Papanicolaou GN. A new procedure for staining vaginal smears. Science 1942; 95:438-9.
Haroske G, Baak JP, Danielsen H, Giroud F, Gschwendtner A, Oberholzer M, Reith A, Spieler P, Böcking A. Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol 2001; 23:89-95.
Montironi R, Diamanti L, Santinelli A, Magi Galluzzi C, Scarpelli M, Giannulis I, Mangili F. Computed cell cycle and DNA histogram analyses in image cytometry in breast cancer. Clin Pathol 1993; 46:795-800.
Jimenez O, Timms A, Quirke P. Prognosis in malignant glioma: A retrospective study of biopsy specimens by flow cytometry. Neuropathol Appl Neurobiol 1989; 15:331-8.
Danova M, Giaretti W, Merlo F. Prognostic significance of nuclear DNA content in human neuroepithelial tumors. Int J Cancer 1991; 48:663-7.
Taylor SR, Blatt J, Costantino JP, Roederer M, Murphy RF. Flow cytometric DNA analysis of Neuroblastoma and Ganglioneuroma. A 10-year retrospective study. Cancer 1988; 62:749-54.
Reavey-Cantwell J, Haroun RI, Zahurak M, Clatterbuck RE, Parker RJ, Mehta R, Fruehauf JP, Brem H. The prognostic value of tumor markers in patients with glioblastoma multiforme: Analysis of 32 patients and review of the literature. Journal of Neuro - Oncology 2001; 55(3):195-204.
Ellen Greenebaum, Leopold G. Koss, Andrew B. Sherman, Flora Elequin. Comparison of needle aspiration and solid biopsy technics in the flow cytometric study of DNA distributions of surgically resected tumors. American Journal of Clinical Pathology 1984; 82(5):559- 64.