Immunohistochemical Classification of Primary and Secondary Glioblastomas
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Background: Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. Methods: We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. Results: According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/ p53(–), IDH-1(–)/EGFR(+)/p53(–), and EGFR(–)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(–)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(–)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(–) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(–) was best for identifying S-GBLs. Conclusions: We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.
Abstract
Background: Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. Methods: We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. Results: According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/ p53(–), IDH-1(–)/EGFR(+)/p53(–), and EGFR(–)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(–)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(–)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(–) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(–) was best for identifying S-GBLs. Conclusions: We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.
참고문헌 (26)
- Ohgaki H, "Genetic pathways to primary and secondary glioblastoma", Am J Pathol, 170, pp.1445~1453 (2007)
- 김영준, "MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour", Journal of Pathology and Translational Medicine, 45(5), pp.455~462 (2011), 대한병리학회
- Peiffer J, "Hans-Joachim Scherer (1906-1945), pioneer in glioma research", Brain Pathol, 9, pp.241~245 (1999)
- Ohgaki H, "Genetic pathways to glioblastoma: a population-based study", Cancer Res, 64, pp.6892~6899 (2004)
- Cancer Genome Atlas Research Network, "Comprehensive genomic characterization defines human glioblastoma genes and core pathways", Nature, 455, pp.1061~1068 (2008)
- von Deimling A, "Subsets of glioblastoma multiforme defined by molecular genetic analysis", Brain Pathol, 3, pp.19~26 (1993)
- Watanabe K, "Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas", Brain Pathol, 6, pp.217~223 (1996)
- Yan H, "IDH1 and IDH2 mutations in gliomas", N Engl J Med, 360, pp.765~773 (2009)
- van den Bent MJ, "IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group", Clin Cancer Res, 16, pp.1597~1604 (2010)
- Sonoda Y, "Analysis of IDH1 and IDH2 mutations in Japanese glioma patients", Cancer Sci, 100, pp.1996~1998 (2009)
- Balss J, "Analysis of the IDH1 codon 132 mutation in brain tumors", Acta Neuropathol, 116, pp.597~602 (2008)
- Takano S, "Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing", Brain Tumor Pathol, 28, pp.115~123 (2011)
- Mellai M, "IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors", J Neurooncol, 105, pp.345~357 (2011)
- 정진행, "Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase Inhibitor Treatment", Journal of Pathology and Translational Medicine, 47(1), pp.52~60 (2013), 대한병리학회
- 김인선, "EGFR Gene Amplification and Protein Expression in Invasive Ductal Carcinoma of the Breast", Journal of Pathology and Translational Medicine, 47(2), pp.107~115 (2013), 대한병리학회
- Das P, "A clinicopathological and molecular analysis of glioblastoma multiforme with long-term survival", J Clin Neurosci, 18, pp.66~70 (2011)
- Mellinghoff IK, "Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors", N Engl J Med, 353, pp.2012~2024 (2005)
- Haas-Kogan DA, "Epidermal growth factor receptor, protein kinase B", Akt, and glioma response to erlotinib, 2005, pp.97, 880~887
- Choe G, "Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype", Clin Cancer Res, 8, pp.2894~2901 (2002)
- Choe G, "Analysis of the phosphatidylinositol 3’-kinase signaling pathway in glioblastoma patients in vivo", Cancer Res, 63, pp.2742~2746 (2003)
- Mischel PS, "DNA-microarray analysis of brain cancer: molecular classification for therapy", Nat Rev Neurosci, 5, pp.782~792 (2004)
- Rong Y, "Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD", activator protein-1 transcriptional activity, 2009, pp.69, 2540~2549
- Benito R, "Primary glioblastomas with and without EGFR amplification: relationship to genetic alterations and clinicopathological features", Neuropathology, 30, pp.392~400 (2010)
- Momota H, "p53 abnormality and tumor invasion in patients with malignant astrocytoma", Brain Tumor Pathol, 27, pp.95~101 (2010)
- Srividya MR, "Age-dependent prognostic effects of EGFR", p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients, 2010, pp.63, 687~691
- Stoczynska-Fidelus E, "Glioblastoma specimens with TP53 mutations do not show EGFRvIII amplification", Cancer Genet, 204, pp.282~283 (2011)
