The Applicability of Haarlem Integrated Diagnostic System in Diffuse Glial Tumors and The Role of PDGFRA Amplification as a Marker of Recurrence and Prognosis

Background: With the help of genetic studies, it is possible to obtain information about diagnosis and prognosis of glial tumors.

Aims: We aimed 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 are prognostic.

Study Design: Diagnostic accuracy study.

Methods: The status of molecular changes proposed by current classifications in 60 cases diagnosed with histologically grade II and grade III oligodendrogliomas, astrocytomas and oligoastrocytomas were evaluated. IDH1 (R132H), ATRX, and p53 antibodies were applied immunohistochemically. The 1p / 19q status and PDGFR-α / CEP4 amplification were evaluated by Fluorescence In Situ Hybridization. The SPSS 21.0 statistical package program was used for the selected tests in the statistical analysis of the findings. Sensitivity, specificity, positive predictive level, negative predictive level, and accuracy rate were evaluated in accordance with the specified threshold levels. The significance value was regarded as p < 0.05.

Results: The diagnosis changed with genetic alterations. Only 1 case (16%) was left in the same diagnosis as anaplastic oligoastrocytoma. The IDH mutation was 97.5% sensitive in oligodendrogliomas,88.8 in astrocytomas. For predicting oligodendroglial tumor, the sensitivity, spesificity, positive predictive value and negative predictive value of the cut-off value for 1p/19q codeletion was 100%. For predicting astrocytic tumor, the sensitivity, spesificity, positive predictive value and negative predictive value of the cut-off values for ATRX mutation were 72.2%, 100%, 100% and 89.1%, respectively, whereas for p53 mutation 77.7%, 95.1%, 87.5% and 90.6%, respectively. PDGFR-α / CEP4 amplification was not detected in any of the cases. Polisomia was detected in 13 (21%) of the cases. These cases were high grade astrocytomas but there was no statistically significant difference between the integrated diagnostic groups according to CEP4 positivity (p=0,157). There was association between IDH 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 with histopathological examination. For the diagnosis of oligodendroglial tumor 1p / 19q codeletion, fort he diagnosis of astrocytic tumor ATRX and p53 mutation should be determined. PDGFRA amplification is more common in high grade glial tumors and is not included in the class of glial tumor with intermediate grade. The presence of IDH mutation and 1p / 19q codeletion in glial tumors is associated with good prognosis.