513P - Cyclin pathway in oligodendrogliomas IDH mut and 1p/19q codeleted

Background

Oligodendrogliomas (OLIG), are rare tumors of the central nervous system. The current WHO classification requires the presence of IDH mutation and 1p/19q codeletion. Grade 3 OLIG presents a higher number of chromosomal alterations than grade 2, indicating that progression to malignancy is associated with the acquisition of multiple genetic abnormalities. An increased incidence of deletions in the short arm of chromosome 9 has been found. CDKN2A is located on chromosome 9 and encodes for 2 proteins p16 (or p16INK4a) and p14arf. Previous studies have found CDKN2A involvement at 9p21 with homozygous deletion in 25% of grade 3 oligodendrogliomas. Many of these studies were performed in a series of patients with OLIG diagnosed by histopathological criteria, but not by current molecular criteria. This study analyzed the cyclin pathway in a series of oligodendrogliomas with IDH mutation and 1p/19q codeletion.

Methods

Cases with a morphological diagnosis of oligodendroglioma were identified (182 cases). This same cohort was subsequently reclassified according to current WHO criteria (91 cases). The median follow-up of this case series was 9 years. In the reclassified cohort, p16, pRb and D1 cyclin were studied by immunohistochemistry.

Results

There was no p16 expression in 16 of 71 cases (22.5%). The absence of expression was significantly associated with a worse prognosis. Median OS in the absence of p16 of 9 years (95%IC 9.36-17.35) vs 13.35 years when there was p16 expression (95%IC 9.36-17.35) p=0.023 HR 0.41. In grade 2 oligodendrogliomas, the median OS was 10.86 vs 13.35 p=0.754, and in grade 3, 4.76 vs 17.49 p=0.010. According to a multivariate analysis including data on the extent of surgery, tumor grade, adjuvant treatment, and p16, only the absence of p16 showed a statistically significant prognostic value (p=0.034). There was no correlation between the loss of p16 and the presence of microvascular proliferation, necrosis, or uptake on MRI. In grade 2 oligodendrogliomas, high cyclin D1 expression was associated with worse survival; 12.3 vs 0.78 years (p=0.001).

Conclusions

Loss of p16 is more frequent in grade 3 than in grade 2 oligodendrogliomas and is associated with worse survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.A. Vaz Salgado: Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal and Institutional, Coordinating PI: Pfizer. J.M. Sepulveda Sanchez: Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: MSD, Novocure, CeCaVa, Cantex; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Cantex. A. Carrato Mena: Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Bayer, Merck, MSD, Novartis, Shire. L.L. Ley: Non-Financial Interests, Member, President: Sociedad Española de Neurocirugía; Non-Financial Interests, Member: Grupo Español de Investigaciones Neurooncológicas. All other authors have declared no conflicts of interest.