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Grade IV Glial Tümörlerde, Mitotik Aktivite, Ki-67 ve Platelet Volüm İndeksinin Prognostik Belirteç Olarak Karşılaştırılması

Year 2019, Volume: 72 Issue: 2, 222 - 226, 02.10.2019

Tolga Turan Dundar

Abstract

Amaç: Tanı anında kayıt edilen platelet sayısındaki artış, gliablastoma ve diğer intrakraniyal patolojiler için bağımsız bir risk faktörüdür ve kötü prognoz göstergesidir. Tümör mikro-dolaşımı kaynaklı, birçok sitokin ve faktörlerin salınması sonucu plateletlerin aktive olması ve nöroenflamasyonda aktif rol oynaması bu hipotezin temelini oluşturur. Glial tümörlerde proliferasyon göstergesi olarak, Ki-67 indeksi ve mitotik aktivite sıklıkla kullanılmaktadır. Glial tümörlerde,yüksek Ki-67 indeks oranı ve mitotik aktivite agresif klinik progresyon,vasküler invazyon ve kötü prognoz ile karakterizedir. Ortalama platelet hacminin platelet sayımına oranı olan platelet volüm indeksini (PVİ), birçok intrakraniyal patolojilerde prognostik faktör olarak kullanılmasını öneren çalışmalarda artış mevcuttur. Bu çalışma da ilk defa PVİ, immün yanıt belirteci olarak, Ki-67 ve mitotik ativite ile karşılaştırdık. Böylelikle, hızlı hesaplanabilen ve de düşük maliyetli yeni bir prognostik faktörü ortaya koymayı amaçladık.

Gereç ve Yöntem: Girişimsel olmayan klinik çalışma için etik kurul onayı alındıktan sonra – son iki yıl içerinde dahil edilme kriterlerini sağlayangliablastom multiforme tanısı almış 65 hasta retrospektifolarak değerlendirildi. Rutin patolojik tanı süreçlerinden geçen hastaların Ki-67 indeksi ve mitoz sayısı Kayıt edildi. PVİ, ameliyat öncesi değerlendirme amacı ile yapılan tam kan sayımı testinden platelet sayısı ve hacmi kullanılarak hesaplandı. Çalışma retrospektif olduğu için hiçbir hastanın tedavi sürecini etkilemedi. PVİ; Ortalama platelet hacmi (fL) x100/Platelet sayısı (per 1000) olarak tanımlandı.

Bulgular: PVİ ile Ki-67 ve mitoz sayısı arasında; negatif yönde, zayıf derecede korelasyon bulundu.

Sonuç: Bu çalışma PVİ azalırken, Ki-67 ve mitoz sayısının arttığı ortaya konuldu. Yüksek gradlı glial tümörlerde PVİ, prognostik ve prediktif bir faktör olarak kullanılabilir. Fakat, yine de bu hipotezimizin, daha çok olgu sayısı ve tümör alt gruplarını da ortaya koyan çalışmalara ihtiyacı vardır.

Keywords

Gliablastoma GBM Platelet Ortalama Platelet Hacmi Platelet Volüm İndeksi PVİ

Ethical Statement

Etik Kurul Onayı: Bu çalışma, Bezmialem Vakıf Üniversitesi Klinik Olmayan Etik Kurul tarafından onaylanmıştır (2018.876). Hasta Onayı: Retrospektif veri analiz çalışmasıdır. Hiçbir hastanın tanı ve tedavi sürecinde bir değişiklik yapmamıştır. Hasta onamları alınmıştır. Hakem Değerlendirmesi: Editörler kurulu ve editörler kurulu dışında olan kişiler tarafından değerlendirilmiştir. Finansal Destek: Yazar finansal destek almadığını beyan eder.

Supporting Institution

-

Project Number

-

Thanks

Patolojik tanı ve verilerin elde edilmesinde, literatür taramasında büyük katkısı olan Bezmialem Vakıf Üniversitesi Patoloji Anabilim Dalı’ndan Uzm. Dr. Ganime Çoban’a sonsuz teşekkürlerimi sunarım.

References

  • 1. Gusyatiner O, Hegi ME. Glioma epigenetics: From subclassification to novel treatment options. Semin Cancer Biol. 2018;51:50-58.
  • 2. Mineo M, Ricklefs F, Rooj AK. The Long Non-coding RNA HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches. Cell Rep. 2016;15:2500-2509.
  • 3. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumours of the Central Nervous System: a summary: Acta Neuropathol 2016;131:803-820.
  • 4. Kaynar MY, Dündar TT. Düşük Dereceli Gliomalar ve Tedavileri, Ozyurt ME editör. Beyin Tümörleri Kök Hücresi ve Tümerogenezisi. Cilt 1, Birinci Baskı, İstanbul: 2015;239-251.
  • 5. Stoyanov GS, Dzhenkov DL, Kitanova M, et al. Correlation Between Ki- 67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation. Cureus. 2017;26;9:e1396.
  • 6. Wong E, Nahar N, Hau E, et al . Cut‐point for Ki‐67 proliferation index as a prognostic marker for glioblastoma. Asia Pac J Clin Oncol. 2019;15:5-9.
  • 7. Hirashima Y, Hamada H, Kurimoto M, et al. Decrease in platelet count as an independent risk factor for symptomatic vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2005;102:882-887.
  • 8. Zhou Y, Jiang Y, Peng Y, et al. The Quantitative and Functional Changes of Postoperative Peripheral Blood Immune Cell Subsets Relate to Prognosis of Patients with Subarachnoid Hemorrhage: A Preliminary Study. WorldNeurosurgery. 2017;206-215.
  • 9. Ray B, Tinsley L, Ford L, et al. Trends of Platelet Volume Index Predicts Delayed Cerebral Ischemia after Subarachnoid Hemorrhage. World Neurosurg. 2018;624-631.
  • 10. Alvarez de Eulate-Beramendi S, Alvarez-Vega MA, Balbin M, et al. Prognostic factors and survival study in high-grade glioma in the elderly. Br J Neurosurg. 2016;30:330-336. 11. Sarıca FB, Yademir F, Cekinmez M, et al. “Yeni Tanı Almış Glioblastoma Hastalarında Temozolomid ile Yapılan Konkomitan Terapi ve Nüks Glioblastoma Olgularında Uygulanan Bevacizumab ve İrinotecan Antianjiyojenik Kombinasyon Terapisi Etkinliği: 10 Yıllık Tedavi Sonuçları”. Türk Nöroşirürji Derg. 2015;1:19-30.
  • 12. Chen WJ, He DS, Tang RX, et al. ChenKi-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis Asian Pac J Cancer Prev. 2015;411-420.
  • 13. Moskowitz SI, JinPrayson T. RA Role of MIB1 in predicting survival in patients with glioblastomas .J Neurooncol. 2006;76:193-200.
  • 14. Kanyılmaz G, Önder H, Aktan M, et al. Prognostic Importance of Ki-67 Labeling Index in Grade II Glial Tumors. Turk J Oncol. 2018;33:48-53.
  • 15. Lin Y, Zhou J, Xu J, et al. Effects of combined radiosurgery and temozolomide therapy on epidermal growth factor receptor and variant III in glioblastoma multiforme. Oncol Lett. 2018;15:5751-5759.
  • 16. Charles N, Holland EC . The perivascular niche microenvironment in brain tumor progression. Cell Cycle. 2010; 9:3012-3021.
  • 17. Charles NA, Holland EC, Gilbertson R, et al. The brain tumor microenvironment. Glia 2012;60:502-514.
  • 18. Marx S, Splittstöhser M, Kinnen F, et al. Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients. Oncotarget. 2018;25;9:25860-25876.
  • 19. Brockmann MA, Bender B, Plaxina E, et al. Differential effects of tumorplatelet interaction in vitro and in vivo in glioblastoma. J Neurooncol. 2011;105:45-56.
  • 20. Nolte I, Przibylla H, Bostel T, et al. Tumor-platelet interactions: glioblastoma growth is accompanied by increasing platelet counts. Clin Neurol Neurosurg. 2008;110:339-342.
  • 21. Mills SJ, du Plessis D, Pal P, et al. Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging. AJNR Am J Neuroradiol. 2015;37:811-817.
  • 22. Nielsen LAG, Bangsø JA, Lindahl KH, et al. Evaluation of the proliferation marker Ki-67 in gliomas: Interobserver variability and digital quantification. Diagn Pathol. 2018;13:38-46.

Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas

Year 2019, Volume: 72 Issue: 2, 222 - 226, 02.10.2019

Tolga Turan Dundar

Abstract

Objectives: An elevated platelet count is considered an independent prediction of survey in glioblastoma and various other intracranial entities. Activity of the tumor microcirculation resulting in platelet activation and release of several cytokines and factors from activated platelets has been suggested to play an active role in neuro-inflammation. Ki-67 index and mitotic activity are markers which could be showed proliferation in the glial tumor. High Ki-67 expression and mitosis rate of high grade glial tumors have been more aggressive clinical progression, poor prognosis, more vascular invasion than low. Recently, Mean Platelet Volume (MPV) to platelet count (PLT) ratio has become a trend indicator to anticipate the outcome of a patient suffering from intracranial pathologies. The study aims to determine first time whether the comparison of the Volume Index (PVI) as an immune response marker with the Ki-67 and mitotic activity could be used as a prognostic factor in gliablastoma (WHO Grade IV)

Materials and Methods: In the retrospective study, we studied 65 patients diagnosed with glioblastoma who had inclusion and exclusion criteria. The correlation between PVI, Ki-67 and mitotic activity was examined all cases after pathologically diagnosed, by the routine processes of the pathological preparates. PVI was calculated from pre-operative first complete blood count (CBC) and was defined as MPV value (fL)x100/PLT (per 1000). The Kolmogorov-Smirnov test and Spearman’s correlation coefficient was used in the analysis of the interrelationship.

Results: The correlation between the PVI, Ki-67 and mitotic index was found to be leak statistically correlation.

Conclusion: It was determined that PVI is decreased, Ki-67 immunoreactivity and mitotic index are increased. The PVI may be used as a prognostic, predictive factor for glioblastoma. Nevertheless, further studies concerning the prognosis of glioblastoma are needed to confirm this hypothesis.

Keywords

Glioblastoma GBM Platelets Mean Platelet Volume Platelet Volume Index PVI

Ethical Statement

-

Supporting Institution

-

Project Number

-

Thanks

-

References

  • 1. Gusyatiner O, Hegi ME. Glioma epigenetics: From subclassification to novel treatment options. Semin Cancer Biol. 2018;51:50-58.
  • 2. Mineo M, Ricklefs F, Rooj AK. The Long Non-coding RNA HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches. Cell Rep. 2016;15:2500-2509.
  • 3. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumours of the Central Nervous System: a summary: Acta Neuropathol 2016;131:803-820.
  • 4. Kaynar MY, Dündar TT. Düşük Dereceli Gliomalar ve Tedavileri, Ozyurt ME editör. Beyin Tümörleri Kök Hücresi ve Tümerogenezisi. Cilt 1, Birinci Baskı, İstanbul: 2015;239-251.
  • 5. Stoyanov GS, Dzhenkov DL, Kitanova M, et al. Correlation Between Ki- 67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation. Cureus. 2017;26;9:e1396.
  • 6. Wong E, Nahar N, Hau E, et al . Cut‐point for Ki‐67 proliferation index as a prognostic marker for glioblastoma. Asia Pac J Clin Oncol. 2019;15:5-9.
  • 7. Hirashima Y, Hamada H, Kurimoto M, et al. Decrease in platelet count as an independent risk factor for symptomatic vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2005;102:882-887.
  • 8. Zhou Y, Jiang Y, Peng Y, et al. The Quantitative and Functional Changes of Postoperative Peripheral Blood Immune Cell Subsets Relate to Prognosis of Patients with Subarachnoid Hemorrhage: A Preliminary Study. WorldNeurosurgery. 2017;206-215.
  • 9. Ray B, Tinsley L, Ford L, et al. Trends of Platelet Volume Index Predicts Delayed Cerebral Ischemia after Subarachnoid Hemorrhage. World Neurosurg. 2018;624-631.
  • 10. Alvarez de Eulate-Beramendi S, Alvarez-Vega MA, Balbin M, et al. Prognostic factors and survival study in high-grade glioma in the elderly. Br J Neurosurg. 2016;30:330-336. 11. Sarıca FB, Yademir F, Cekinmez M, et al. “Yeni Tanı Almış Glioblastoma Hastalarında Temozolomid ile Yapılan Konkomitan Terapi ve Nüks Glioblastoma Olgularında Uygulanan Bevacizumab ve İrinotecan Antianjiyojenik Kombinasyon Terapisi Etkinliği: 10 Yıllık Tedavi Sonuçları”. Türk Nöroşirürji Derg. 2015;1:19-30.
  • 12. Chen WJ, He DS, Tang RX, et al. ChenKi-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis Asian Pac J Cancer Prev. 2015;411-420.
  • 13. Moskowitz SI, JinPrayson T. RA Role of MIB1 in predicting survival in patients with glioblastomas .J Neurooncol. 2006;76:193-200.
  • 14. Kanyılmaz G, Önder H, Aktan M, et al. Prognostic Importance of Ki-67 Labeling Index in Grade II Glial Tumors. Turk J Oncol. 2018;33:48-53.
  • 15. Lin Y, Zhou J, Xu J, et al. Effects of combined radiosurgery and temozolomide therapy on epidermal growth factor receptor and variant III in glioblastoma multiforme. Oncol Lett. 2018;15:5751-5759.
  • 16. Charles N, Holland EC . The perivascular niche microenvironment in brain tumor progression. Cell Cycle. 2010; 9:3012-3021.
  • 17. Charles NA, Holland EC, Gilbertson R, et al. The brain tumor microenvironment. Glia 2012;60:502-514.
  • 18. Marx S, Splittstöhser M, Kinnen F, et al. Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients. Oncotarget. 2018;25;9:25860-25876.
  • 19. Brockmann MA, Bender B, Plaxina E, et al. Differential effects of tumorplatelet interaction in vitro and in vivo in glioblastoma. J Neurooncol. 2011;105:45-56.
  • 20. Nolte I, Przibylla H, Bostel T, et al. Tumor-platelet interactions: glioblastoma growth is accompanied by increasing platelet counts. Clin Neurol Neurosurg. 2008;110:339-342.
  • 21. Mills SJ, du Plessis D, Pal P, et al. Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging. AJNR Am J Neuroradiol. 2015;37:811-817.
  • 22. Nielsen LAG, Bangsø JA, Lindahl KH, et al. Evaluation of the proliferation marker Ki-67 in gliomas: Interobserver variability and digital quantification. Diagn Pathol. 2018;13:38-46.
There are 21 citations in total.

Details

Primary Language English
Subjects Brain and Nerve Surgery (Neurosurgery)
Journal Section Articles
Authors

Tolga Turan Dundar 0000-0003-0030-2618

Project Number -
Publication Date October 2, 2019
Published in Issue Year 2019 Volume: 72 Issue: 2

Cite

APA Dundar, T. T. (2019). Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 72(2), 222-226. https://doi.org/10.4274/atfm.galenos.2019.93584
AMA Dundar TT. Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas. Ankara Üniversitesi Tıp Fakültesi Mecmuası. October 2019;72(2):222-226. doi:10.4274/atfm.galenos.2019.93584
Chicago Dundar, Tolga Turan. “Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index As a Prognostic Marker in Gliablastomas”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 72, no. 2 (October 2019): 222-26. https://doi.org/10.4274/atfm.galenos.2019.93584.
EndNote Dundar TT (October 1, 2019) Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas. Ankara Üniversitesi Tıp Fakültesi Mecmuası 72 2 222–226.
IEEE T. T. Dundar, “Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 72, no. 2, pp. 222–226, 2019, doi: 10.4274/atfm.galenos.2019.93584.
ISNAD Dundar, Tolga Turan. “Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index As a Prognostic Marker in Gliablastomas”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 72/2 (October 2019), 222-226. https://doi.org/10.4274/atfm.galenos.2019.93584.
JAMA Dundar TT. Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2019;72:222–226.
MLA Dundar, Tolga Turan. “Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index As a Prognostic Marker in Gliablastomas”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 72, no. 2, 2019, pp. 222-6, doi:10.4274/atfm.galenos.2019.93584.
Vancouver Dundar TT. Comparasion Between Mitotic Activity, Ki-67 Index and Platelet Volume Index as a Prognostic Marker in Gliablastomas. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2019;72(2):222-6.
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