Immunohistochemical expression of ATRX in gliomas

Jalal Ali Jalal; Anjam Ibrahim Sulaiman Rowandizy; Ava Taher Ismael

doi:10.14715/cmb/2020.66.7.20

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Vol. 66 No. 7: Issue 7

Issue Published : November 9, 2020

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Immunohistochemical expression of ATRX in gliomas

https://doi.org/10.14715/cmb/2020.66.7.20

Jalal Ali Jalal

Department of Basic Sciences/Pathology, College of Medicine, Hawler Medical University, Erbil, Kurdistan Region-Iraq

Anjam Ibrahim Sulaiman Rowandizy

Department of Surgery, College of Medicine, Hawler Medical University, Erbil, Kurdistan Region-Iraq

Ava Taher Ismael

Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region-Iraq

Corresponding Author(s) : Jalal Ali Jalal

jajpishdary@gmail.com

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7
Article Published : August 31, 2020

Abstract

Glioma is one of the primary tumors of the central nervous system that occurs in the spinal cord or brain and the origin of the tumor is from glial cell cells. The most common site of glioma tumors is the brain. Glioma accounts for 30% of all central nervous system tumors and 80% of malignant brain tumors. Alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutations are frequently distinguished in gliomas. Current research is an attempt to assess ATRX immunoexpression in different types of gliomas diagnosed, in Erbil-Iraq, and to evaluate its association with patient's age, gender, tumor location, grade and type. From January 2015 to January 2017, we reviewed and analyzed 97 cases of glioma. Immunohistochemical staining, for ATRX, was performed using an automated immunostainer technique. According to the WHO grading system for brain tumors, 16 (16.5%) cases were grade I gliomas, 27 (27.8%) were grade II, 10 (10.3%) were anaplastic gliomas (grade III), and 44 (45.3%) cases were glioblastomas WHO (grade IV). Positive ATRX immunoexpression was demonstrated in 27 (27.8%) cases. The highest rates of ATRX expression (55.6%) were among 30-39 years' age group, supratentorial (34.2%), and among grade II and III tumors (40.7% and 30% respectively). A significant association was observed between ATRX expression and patient's age, tumor location, tumor type and grade (p-values 0.010, 0.004, 0.004, and 0.037 respectively). No significant association was found between ATRX expression and patient's gender (p-value 0.097). It was found that ATRX is frequently expressed in grade II and III astrocytomas and was significantly related to the patient's age, tumor location, type and grade, so it can be used as a good diagnostic and prognostic indicator for glioma.

Keywords

Glioma ATRX Immunohistochemistry.

Jalal, J. A., Rowandizy, A. I. S., & Ismael, A. T. (2020). Immunohistochemical expression of ATRX in gliomas. Cellular and Molecular Biology, 66(7), 131–135. https://doi.org/10.14715/cmb/2020.66.7.20

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References

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. WHO classification of tumours of the central nervous system. 4th ed. Lyon, France: IARC Press, 2007.
Burger PC, Scheithauer BW, Paulus W, et al. Pilocytic astrocytoma. In: Kleihues P, Cavenee WK, eds. Pathology and genetics of tumours of the nervous system. Lyon, France: IARC Press, 2000:45-51.
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987-96.
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008; 359:492-507. [Erratum, N Engl J Med 2008; 359:877.
Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and followup. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2014; 25 Suppl 3:iii93-101.
Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol 2012; 124:615–25.
Kannan K, Inagaki A, Silber J, et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012; 3:1194–203.
Haberler C, Wöhrer A. ATRX, a new candidate biomarker in gliomas. Clin Neuropathol 2014 33(2):108–111.
Reuss DE, Sahm F, Schrimpf D, et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 2015; 129:133–46.
Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, Wilde RF et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 2012; 3: 710-722.
Killela PJ, Reitman ZJ, Jiao Y et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013; 110: 6021-6026
Weisbrod AB, Zhang L, Jain M, Barak S, Quezado MM & Kebebew E. Altered PTEN, ATRX, CHGA, CHGB, and TP53 Expression Are Associated with Aggressive VHL-Associated Pancreatic Neuroendocrine Tumors. Hormones & cancer 2013; 4:165–75.
Lacayo NJ, Meshinchi S, Kinnunen P, Yu R, Wang Y, et al. Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes. Blood 2004; 104:2646–54.
Liu N, Wang PF, Song HW, Kong LW, Yao K, Qi XL, et al. Immunostaining of IDH-1R132H and ATRX proteins in the classification of adult glioblastomas. Int J Clin Exp Pathol 2016; 9(12):12849-12854.
Ebrahimi A, Skardelly M, Bonzheim I, Ott I, Mühleisen H , Eckert F etal. ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta Neuropathol Commun 2016; 4:60
Wiestler B, Capper D, Holland Letz T, Korshunov A, Deimling A, Pfister SM, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 2013 126:443–451.
Parsons DW, Jones S, Zhang X, Cheng-Ho Lin J, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiform. Science 2008; 321:1807–12.
Ikemura M, Shibahara J, Mukasa A, Takayanagi S, Aihara K, Saito N et al. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology 2016; DOI: 10.1111/his.12927
Cardona AF, Rojas L, Wills B, Behaine J, Jimenez E, Hakim F et al. Genotyping low-grade gliomas among Hispanics. Neuro-Oncology Practice 2016 3(3), 164–172.
Yamamichi A, Ohka F, Aoki K, Suzuki H, Kato A, Hirano M. Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion. Brain Tumor Pathol 2018; https://doi.org/10.1007/s10014-018-0312-5.
Chatterjee D, Radotra BD, Kumar N, Vasishta RK, Gupta SK. IDH1, ATRX, and BRAFV600E mutation in astrocytic tumors and their significance in patient outcome in north Indian population. Surg Neurol Int 2018; 9:29.
Mur P, Mollejo M, Hernandez-Iglesias T, Rodrı´guez de Lope A, Castresana JS, Garcı´a JF et al. Molecular Classification Defines 4 Prognostically Distinct Glioma Groups Irrespective of Diagnosis and Grade. J Neuropathol Exp Neurol 2015; 74, 3, 241- 49.
Omer NS, Jalal AJ, Ismael AT. IDH1 (R132H) Immunoexpression in Glioma. JKBMS 2018; 4, 1, 57-63.
Cai J, Zhang C, Zhang W, Wang G, Yao K, Wang Z et al. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors. Oncoscience 2016; 3 (7-8).
Ostrom QT, Kinnersley B, Wrensch MR, Eckel-Passow JE, Armstrong G, Rice T et al. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Scientific Reports 2018; 8:7352 | DOI: 10.1038/s41598-018-24580-z.
Cai J, Zhu P, Zhang C, Li Q, Wang Z, Li G et al. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget 2016; 7, 13, 16384-95.
Takano S, Ishikawa E, Sakamoto N, Matsuda M, Akutsu H, Noguchi M et al. Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas. Brain Tumor Pathol 2016; DOI 10.1007/s10014-016-0260-x.
Lehtinen A, Raita A, Kesseli J, Annala M, Nordfors K, Yli-Harja O et al. Clinical association analysis of ependymomas and pilocytic astrocytomas reveals elevated FGFR3 and FGFR1 expression in aggressive ependymomas. 2017; BMC Cancer 17:310 DOI 10.1186/s12885-017-3274-9.

References

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. WHO classification of tumours of the central nervous system. 4th ed. Lyon, France: IARC Press, 2007.

Burger PC, Scheithauer BW, Paulus W, et al. Pilocytic astrocytoma. In: Kleihues P, Cavenee WK, eds. Pathology and genetics of tumours of the nervous system. Lyon, France: IARC Press, 2000:45-51.

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

Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008; 359:492-507. [Erratum, N Engl J Med 2008; 359:877.

Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and followup. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2014; 25 Suppl 3:iii93-101.

Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol 2012; 124:615–25.

Kannan K, Inagaki A, Silber J, et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012; 3:1194–203.

Haberler C, Wöhrer A. ATRX, a new candidate biomarker in gliomas. Clin Neuropathol 2014 33(2):108–111.

Reuss DE, Sahm F, Schrimpf D, et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 2015; 129:133–46.

Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, Wilde RF et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 2012; 3: 710-722.

Killela PJ, Reitman ZJ, Jiao Y et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013; 110: 6021-6026

Weisbrod AB, Zhang L, Jain M, Barak S, Quezado MM & Kebebew E. Altered PTEN, ATRX, CHGA, CHGB, and TP53 Expression Are Associated with Aggressive VHL-Associated Pancreatic Neuroendocrine Tumors. Hormones & cancer 2013; 4:165–75.

Lacayo NJ, Meshinchi S, Kinnunen P, Yu R, Wang Y, et al. Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes. Blood 2004; 104:2646–54.

Liu N, Wang PF, Song HW, Kong LW, Yao K, Qi XL, et al. Immunostaining of IDH-1R132H and ATRX proteins in the classification of adult glioblastomas. Int J Clin Exp Pathol 2016; 9(12):12849-12854.

Ebrahimi A, Skardelly M, Bonzheim I, Ott I, Mühleisen H , Eckert F etal. ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta Neuropathol Commun 2016; 4:60

Wiestler B, Capper D, Holland Letz T, Korshunov A, Deimling A, Pfister SM, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 2013 126:443–451.

Parsons DW, Jones S, Zhang X, Cheng-Ho Lin J, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiform. Science 2008; 321:1807–12.

Ikemura M, Shibahara J, Mukasa A, Takayanagi S, Aihara K, Saito N et al. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology 2016; DOI: 10.1111/his.12927

Cardona AF, Rojas L, Wills B, Behaine J, Jimenez E, Hakim F et al. Genotyping low-grade gliomas among Hispanics. Neuro-Oncology Practice 2016 3(3), 164–172.

Yamamichi A, Ohka F, Aoki K, Suzuki H, Kato A, Hirano M. Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion. Brain Tumor Pathol 2018; https://doi.org/10.1007/s10014-018-0312-5.

Chatterjee D, Radotra BD, Kumar N, Vasishta RK, Gupta SK. IDH1, ATRX, and BRAFV600E mutation in astrocytic tumors and their significance in patient outcome in north Indian population. Surg Neurol Int 2018; 9:29.

Mur P, Mollejo M, Hernandez-Iglesias T, Rodrı´guez de Lope A, Castresana JS, Garcı´a JF et al. Molecular Classification Defines 4 Prognostically Distinct Glioma Groups Irrespective of Diagnosis and Grade. J Neuropathol Exp Neurol 2015; 74, 3, 241- 49.

Omer NS, Jalal AJ, Ismael AT. IDH1 (R132H) Immunoexpression in Glioma. JKBMS 2018; 4, 1, 57-63.

Cai J, Zhang C, Zhang W, Wang G, Yao K, Wang Z et al. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors. Oncoscience 2016; 3 (7-8).

Ostrom QT, Kinnersley B, Wrensch MR, Eckel-Passow JE, Armstrong G, Rice T et al. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Scientific Reports 2018; 8:7352 | DOI: 10.1038/s41598-018-24580-z.

Cai J, Zhu P, Zhang C, Li Q, Wang Z, Li G et al. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget 2016; 7, 13, 16384-95.

Takano S, Ishikawa E, Sakamoto N, Matsuda M, Akutsu H, Noguchi M et al. Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas. Brain Tumor Pathol 2016; DOI 10.1007/s10014-016-0260-x.

Lehtinen A, Raita A, Kesseli J, Annala M, Nordfors K, Yli-Harja O et al. Clinical association analysis of ependymomas and pilocytic astrocytomas reveals elevated FGFR3 and FGFR1 expression in aggressive ependymomas. 2017; BMC Cancer 17:310 DOI 10.1186/s12885-017-3274-9.

Author biographies is not available.