Impact of CD133 positive stem cell proportion on survival in patients with glioblastoma multiforme

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Background. The aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients.

Patients and methods. Patients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival.

Results. The proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0-11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6-10.5) and 12.0 months (95% CI 9.3-14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0-3.8, p = 0.04).

Conclusions. In patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radiotherapy should be clarified in further studies.

1. Crocetti E, Trama A, Stiller C, Caldarella A, Soffietti R, Jaal J, et al. Epidemiology of glial and non-glial brain tumors in Europe. Eur J Cancer 2012; 48: 1532-42.

2. Lee CH, Jung KW, Yoo H, Park S, Lee SH. Epidemiology of primary brain and central nervous system tumors in Korea. J Korean Neurosurg Soc 2010; 48: 145-52.

3. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987-96.

4. Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978; 49: 333-43.

5. Minniti G, Amelio D, Amichetti M, Salvati M, Muni R, Bozzao A, et al. Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiother Oncol 2010; 97: 377-81.

6. Kase M, Vardja M, Lipping A, Asser T, Jaal J. Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme. RadiotherOncol 2011; 101: 127-31.

7. Mannino M, Chalmers AJ. Radioresistance of glioma stem cells: intrinsic characteristic or property of the ‘microenvironment-stem cell unit’? MolOncol 2011; 5: 374-86.

8. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444: 756-60.

9. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumor initiating cells. Nature 2004; 432: 396-401.

10. Laks DR, Visnyei K, Kornblum HI. Brain tumor stem cells as therapeutic targets in models of glioma. Yonsei Med J 2010; 51: 633-40.

11. Dell’Albani P. Stem cell markers in gliomas. Neurochem Res 2008; 33: 2407-15.

12. Pallini R, Ricci-Vitiani L, Banna GL, Signore M, Lombardi D, Todaro M, et al. Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 2008; 14: 8205-12.

13. Pallini R, Ricci-Vitiani L, Montano N, Mollinari C, Biffoni M, Cenci T, et al. Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis. Cancer 2011; 117: 162-74.

14. Hermansen SK, Christensen KG, Jensen SS, Kristensen BW. Inconsistent immunohistochemical expression patterns of four different CD133 antibody clones in glioblastoma. J Histochem Cytochem 2011; 59: 391-407.

15. Pistollato F, Abbadi S, Rampazzo E, Persano L, Della Puppa A, Frasson C, et al. Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells 2010; 28: 851-62.

16. Sheehan JP, Shaffrey ME, Gupta B, Larner J, Rich JN, Park DM. Improving the radiosensitivity of radioresistant and hypoxic glioblastoma. Future Oncol 2010; 6: 1591-1601.

17. Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. NeuroOncol 2003; 5: 79-88.

18. Metellus P, Nanni-Metellus I, Delfino C, Colin C, Tchogandjian A, Coulibaly B, et al. Prognostic impact of CD133 mRNA expression in 48 glioblastoma patients treated with concomitant radiochemotherapy: a prospective patient cohort at a single institution. Ann Surg Oncol 2011; 18: 2937-45.

19. Ardebili SY, Zajc I, Gole B, Campos B, Herold-Mende C, Drmota S, et al. CD133/prominin 1 is prognostic for GBM patients survival, but inversely correlated with cysteine cathepsins expression in glioblastoma derived spheroids. Radiol Oncol 2011; 45: 102-15.

20. Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z, et al. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res 2008; 27: 85.

21. Joo KM, Kim SY, Jin X, Song SY, Kong DS, Lee JI, et al. Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. Lab Invest 2008; 88: 808-15.

22. Jamal M, Rath BH, Tsang PS, Camphausen K, Tofilon PJ. The brain microenvironment preferentially enhances the radioresistance of CD133(+) glioblastoma stem-like cells. Neoplasia 2012; 14: 150-58.

23. McCord AM, Jamal M, Williams ES, Camphausen K, Tofilon PJ. CD133+ glioblastoma stem-like cells are radiosensitive with a defective DNA damage response compared with established cell lines. Clin Cancer Res 2009; 15: 5145-53.

24. Jamal M, Rath BH, Williams ES, Camphausen K, Tofilon PJ. Microenvironmental regulation of glioblastoma radioresponse. Clin CancerRes 2010; 16: 6049-59.

25. Christensen K, Schroder HD, Kristensen BW. CD133+ niches and single cells in glioblastoma have different phenotypes. J Neurooncol 2011; 104: 129-43.

26. Schwartzbaum JA, Huang K, Lawler S, Ding B, Yu J, Chiocca EA. Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma. Neuro Oncol 2010; 12: 320-27.

Radiology and Oncology

The Journal of Association of Radiology and Oncology

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