机译
成人弥漫性神经胶质瘤诊断标志物评估模式:欧洲神经病理学会联合会(Euro-CNS)的一项调查
摘要:The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (). Graphical abstract in response to Ramaswamy and Taylor, Cancer Cell 2016 [1].Keywords: diffuse glioma, molecular markers, integrated diagnosis, neuropathology surveyContext
The 2016 update of the WHO classification of tumors of the central nervous system has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information []. This conceptual change has fundamental and far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular findings in large-scale cohort studies to the diagnostic setting of individual patients. Hence, neuropathologists find themselves continuously confronted with the set-up of additional molecular tests as well as the interpretation, validation, and integration of test results. While the proposed integration of molecular markers aims at harmonizing diagnostic standards, it introduces complexity pertaining to technical, personnel, time, and cost-related issues. Adult diffuse glioma comprises the most common group of primary brain tumors and thus, represents a major workload for surgical neuropathologists. It is a prototypic example of a group of tumors that underwent substantial regrouping based on molecular constellations []. Molecular changes such as IDH mutations, 1p19q codeletion, and ATRX mutations are meanwhile considered prerequisites for precise subtyping into diffuse astrocytoma, oligodendroglioma, and glioblastoma categories [, , ]. Likewise, TERT promoter mutations have been implicated as relevant prognostic factors []. Regarding glioblastoma, the MGMT promoter methylation status further impacts therapeutic choices in elderly patients []. All these markers can be assessed on routinely processed formalin-fixed and paraffin-embedded tumor tissues. Two molecular alterations, namely the IDH1 R132H mutation and ATRX mutation with subsequent loss of ATRX protein expression, are mainly evaluated by immunohistochemistry []. All other markers require further molecular techniques such as targeted gene sequencing for IDH2, rare IDH1, and TERT mutations, as well as fluorescence in situ hybridization (FISH) or whole chromosomal arm spanning multiplex ligation-dependent probe amplification (MLPA) for 1p19q codeletion testing []. Likewise, the MGMT promoter methylation status is commonly evaluated using pyrosequencing or methylation-specific polymerase chain reaction (MSP) [, ]. More advanced methods that allow for simultaneous assessment of multiple markers, e.g., brain tumor-associated gene panel sequencing, exome sequencing, or DNA methylation profiling are trending but their availability is still limited to specialized laboratories [, ].