Immunohistochemical expression of Nestin as Cancer Stem Cell Marker in gliomas

Main Article Content

Rasha Mokhtar Abdelkareem
Afaf T Elnashar
Khaled Nasser Fadle
Eman MS Muhammad

Abstract

Background: Gliomas represent the most frequent primary tumors of central nervous system (CNS), contributing to more than half of the incidence of brain tumors. Cancer stem cell markers (CSC) identify a group of patients at high risk for progression. Nestin is an intermediate filament (IF) protein was first described as a neural stem cell/progenitor cell marker. Nestin-positive neuroepithelial stem cells are detected in the subventricular zone of the human adult brain and they remain mitotically active throughout adulthood. The expression of Nestin in gliomas has been suggested to be related to dedifferentiation, improved cell motility, invasive potential and increased malignancy. This study aims to investigate Nestin immunohistochemical expression in different types of glioma and its correlation with different clinicopathological parameters.


Materials and Methods: Nestin immunostaining was studied in 60 specimens of glioma using avidin-biotin peroxidase method.


Results: Nestin was strongly expressed in 11/60 (18.33%), moderately expressed in 29/60 (48.33%) and weekly expressed in 15/60 (25%) of studied gliomas. A significant positive correlation was found between Nestin expression and histologic type (p < 0.001) and increasing grade of gliomas (p < 0.001).


Conclusion: Increased Nestin expression is correlated with tumor progression, increasing grade and poor prognostic parameter of glioma. Nestin is a useful marker for detection of CSC in high-grade glioma which is responsible for resistance to chemo-radiotherapy and may serve as a predictor for patient outcomes.

Article Details

Abdelkareem, R. M., Elnashar, A. T., Fadle, K. N., & Muhammad, E. M. (2019). Immunohistochemical expression of Nestin as Cancer Stem Cell Marker in gliomas. Journal of Neuroscience and Neurological Disorders, 3(2), 162–166. https://doi.org/10.29328/journal.jnnd.1001027
Research Articles

Copyright (c) 2019 Abdelkareem RM, et al.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Tadej S. Prognostic Significance of Immunohistochemical Markers in Glioma Patients. Advances in the Biology, Imaging and Therapies for Glioblastoma. 2011; 284-285.

Sanai N, Chang S, Berger MS. Low grade gliomas in adults. J Neurosurg. 2011; 115: 948-965. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22043865

Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-oncol. 2015; 17: 1-62. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26511214

Ibrahim AS, Khaled HM, Mikhail NNH, Baraka H, Kamel H. Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program. J Cancer Epidemiol. 2014; 437971: 1-18. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25328522

Li SC, Vu LT, Ho HW, Yin HZ, Keschrumrus V, et al. Cancer stem cells from a rare form of glioblastoma multiforme involving neurogenic ventricular wall. Cancer Cell Int. 2012; 12: 41. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22995409

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de TN, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005; 352: 997-1003. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15758010

Bao S, Wu Q, Li Z, Sathornsumetee S, Wang H, et al. Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008; 68: 6043-6048. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18676824

Murre C. Helix–loop–helix proteins and the advent of cellular diversity: 30 years of discovery. Genes & Dev. 2019; 33: 6-25. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30602438

Dahlrot RH, Hermansen SK, Hansen S, Kristensen BW. What is the clinical value of cancer stem cell markers in gliomas? Int J Clin Exp Pathol. 2013; 6: 334-348. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23412423

Zhang M, Song T, Yang L, Chen R, Wu L, et al. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res. 2008; 27: 8. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19108713

Ishiwata T, Matsuda Y, Naito Z. Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis. World J Gastroenterol. 2011; 17: 409-418. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21274370

Dahiya S, Lee da Y, Gutmann DH. Comparative characterization of the human and mouse third ventricle germinal zones. J Neuropathol Exp Neurol. 2011; 70: 622-633. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21666496

Lépinoux-Chambaud C, Eyer J. Review on intermediate filaments of the nervous system and their pathological alterations. Histochem Cell Biol. 2013; 140: 13-22. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23749407

Arai H, Ikota H, Sugawara K, Nobusawa S, Hirato J, et al. Nestin expression in brain tumors: it's utility for pathological diagnosis and correlation with the prognosis of high-grade gliomas. Brain Tumor Pathol. 2012; 29: 160-167.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumors of the Central Nervous System. Revised 4th ED. Lyon: IARC. 2016.

Strojnik T, Rosland GV, Sakariassen PO, Kavalar R, Lah T. Neural stem cell markers, Nestin and musashi proteins, in the progression of human glioma: correlation of Nestin with prognosis of patient survival. Surg Neurol. 2007; 68: 133-143. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17537489

Ma YH, Mentlein R, Knerlich F, Kruse ML, Mehdorn HM, et al. Expression of stem cell markers in human astrocytoma of different WHO grades. J Neurooncol. 2008; 86: 31-45. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17611714

Kitai R, Horita R, Sato K, Yoshida K, Arishima H, et al. Nestin expression in astrocytic tumors delineates tumor infiltration. Brain Tumor Pathol. 2010; 27: 17-21. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20425043

Wan F, Herold-Mende C, Campos B, Centner FS, Dictus C, et al. Association of stem cell-related markers and survival in astrocytic gliomas. Biomarkers. 2011; 16: 136-143. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21323603

Hatanpaa KJ, Hu T, Vemireddy V, Foong C, Raisanen JM, et al. High expression of the stem cell marker Nestin is an adverse prognostic factor in WHO grade II–III astrocytoma and oligoastrocytomas. J Neuro oncol. 2014; 117: 183-189. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24519516

Lin A, Marchionni L, Sosnowski J, Berman D, Eberhart CG, et al. Role of Nestin in glioma invasion. World J Transl Med. 2015; 4: 78-87.

Rani SB, Mahadevan A, Anilkumar SR, Raju TR, Shankar SK. Expression of Nestin - a stem cell associated intermediate filament in human CNS tumors. Indian J Med Res. 2006; 124: 269-280.

Chinnaiyan P, Wang M, Rojiani AM, Tofilon PJ, Chakravarti A, et al. The prognostic value of Nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group. Radiat Oncol. 2008; 3: 32. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18817556

Kim KJ, Lee KH, Kim HS, Moon KS, Jung TY, et al. The presence of stem cell marker-expressing cells is not prognostically significant in glioblastomas. Neuropathology Oct. 2011; 31: 494-502. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21269333