Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. Methods: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. Results: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p < .001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). Conclusions: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
Abstract
Background: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. Methods: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. Results: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p < .001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). Conclusions: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
참고문헌 (20)
- Myung JK, "Prognosis of glioblastoma with oligodendroglioma component is associated with the IDH1 mutation and MGMT methylation status", Transl Oncol, 7, pp.712~719 (2014)[DOI]
- Jiang H, "1p", 19q codeletion and IDH1, Neuro Oncol, pp.2013, 15[DOI]
- Tortosa A, "Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas", Cancer, 97, pp.1063~1071 (2003)[DOI]
- Okamoto Y, "Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas", Acta Neuropathol, 108, pp.49~56 (2004)[DOI]
- Ohgaki H, "Diffuse low-grade gliomas in adults", pp.61~72 (2013), Springer
- Kros JM, "Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p", 19q loss, and correlations with outcome, 2007, pp.66, 545~551
- Killela PJ, "The genetic landscape of anaplastic astrocytoma", Oncotarget, 5, pp.1452~1457 (2014)
- Liu XY, "Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1", IDH2 and TP53 mutations, 2012, pp.124, 615~625
- Louis DN, "WHO classification of tumours of the central nervous system" (2016), IARC Press
- Labussiere M, "All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2", Neurology, 74, pp.1886~1890 (2010)[DOI]
- Louis DN, "International Society of Neuropathology: Haarlem consensus guidelines for nervous system tumor classification and grading", Brain Pathol, 24, pp.429~435 (2014)[DOI]
- Sahm F, "Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma", Acta Neuropathol, 128, pp.551~559 (2014)[DOI]
- Reuss DE, "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, 129, pp.133~146 (2015)[DOI]
- van den Bent MJ, "Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951", J Clin Oncol, 31, pp.344~350 (2013)
- Houillier C, "IDH1 or IDH2 mutations predict longer survival and response to temozolomide in lowgrade gliomas", Neurology, 75, pp.1560~1566 (2010)[DOI]
- Grisold W, "Stroke and cancer: a review", Acta Neurol Scand, 119, pp.1~16 (2009)
- Yan H, "IDH1 and IDH2 mutations in gliomas", N Engl J Med, 360, pp.765~773 (2009)[DOI]
- Haberler C, "Clinical neuropathology practice news 2-2014: ATRX, a new candidate biomarker in gliomas", Clin Neuropathol, 33, pp.108~111 (2014)[DOI]
- Love S, "Greenfield's neuropathology" (2015), CRC Press
- Louis DN, "Comparative study of p53 gene and protein alterations in human astrocytic tumors", J Neuropathol Exp Neurol, 52, pp.31~38 (1993)[DOI]