The Applicability of Haarlem Integrated Diagnostic System in Diffuse Glial Tumors and Molecular Methods Affecting Prognosis

摘要

Background: With the help of genetic studies, it is possible to obtain information about diagnosis and prognosis of glial tumors. Aims: To categorize the cases according to the new World Health Organization Central Nervous System classification by reconsidering the histologic features of oligodendrogliomas, astrocytomas and oligoastrocytomas. We also evaluated whether these genetic features have prognostic significance. Study Design: Diagnostic accuracy study. Methods: Between the years 2011 and 2016, 60 gliomas were examined. Archival material from the Department of Pathology was used for histopathological, immunohistochemical, and molecular analyses. All the cases were classified and graded according to the new 2016 World Health Organization criteria. IDH1 (R132H), alpha thalassemia/mental retardation syndrome, and p53 antibodies were applied immunohistochemically. The 1p/19q status and platelet-derived growth factor receptor-α/CEP4 amplification were evaluated by fluorescence in situ hybridization. After molecular tests, if the diagnosis of oligodendroglioma or astrocytoma is not diagnosed, case should be diagnosed as oligoastrocytoma. Sensitivity, specificity, positive predictive level, negative predictive level, and accuracy rate were evaluated in accordance with the specified threshold levels. Results: Except for 1 case (3.7%), all cases of grade 2 and grade 3 oligoastrocytoma were diagnosed with astrocytoma or oligodendroglioma without any change of grade. Except for 2 case (6.8%), all cases of grade 2 and grade 3 oligodendroglioma were diagnosed oligodendroglioma. All astrocytomas (100%) were given same diagnosis. There is no specific or sensitive test for the diagnosis of oligoastrocytoma. However, 1p/19q codeletion was spesific (100%) and sensitive (100%) for oligodendroglioma. ATRX and p53 mutation showed high spesificity (100% and 95.1% respectively) for diagnosing astrocytoma. Platelet-derived growth factor receptor-α/ CEP4 was not detected in any of the cases. There was association between isocitrate dehydrogenase mutation and 1p/19q loss with longer survival (respectively p=0.147 and p=0.178). Conclusion: In grade 2 and grade 3 glial tumors, pathological diagnosis is not possible only by histological examination. Overall, there was a diagnosis change in 28 cases (46.6%). Especially in cases of oligoastrocytoma, the diagnosis is changed by molecular tests.