# Oligodendrogliomas, cyclin pathway after the introduction of the molecular 2021 World Health Organization (WHO) criteria

## TL;DR

This study shows that loss of p16 expression in oligodendrogliomas is linked to worse survival, especially in higher-grade tumors.

## Contribution

The study confirms the prognostic value of p16 expression in oligodendrogliomas classified by the 2021 WHO molecular criteria.

## Key findings

- Absence of p16 expression is significantly associated with worse overall survival in oligodendrogliomas.
- Loss of p16 is particularly prognostic in Grade 3 oligodendrogliomas.
- High cyclin D1 expression is linked to worse survival in Grade 2 tumors.

## Abstract

In 2016, the World Health Organization (WHO) classification introduced molecular criteria [isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion] for the diagnosis of oligodendroglioma. The cyclin pathway (cyclin-dependent kinase inhibitor 2A deletion/p16 expression) has been extensively studied in this tumour but was performed in series based only on histopathological criteria. This study analysed this pathway in oligodendrogliomas with isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. Cases with morphological diagnosis of oligodendroglioma were identified (182 cases). This same cohort was subsequently reclassified according to the current 2021 World Health Organization (WHO) (91 cases). The type of isocitrate dehydrogenase (IDH) (determined by high-resolution melting and immunohistochemistry) and telomerase reverse transcriptase (TERT) mutations were analysed. Also, p16, pRb and cyclin D1 were studied by immunohistochemistry. In the reclassified cohort, 82 cases (90.1%) had isocitrate dehydrogenase1 (IDH1) mutation and 9 cases (9.9%) had isocitrate dehydrogenase 2 (IDH2) mutation. Eighty cases (87.9%) had TERT mutation, 33 cases (36.3%) had 250T, and 47 cases (51.6%) had C228T mutation. 16 of 71 cases (22.5%) had no p16 expression, and was significantly associated with a worse prognosis; the median OS in the absence of p16 was 9 years (95% CI 9.36–17.35) versus 13.35 years with p16 expression (95% CI 9.36–17.35) P = 0.023 HR 0.41. With a clear difference in Grade 3 (4.76 versus 17.49 years). In a multivariate analysis, only the absence of p16 showed a statistically significant prognostic value (P = 0.034). In Grade 2 oligodendrogliomas, high cyclin D1 expression was associated with worse survival. In this cohort of oligodendroglial tumours classified by molecular criteria, the loss of p16 expression is associated with a poor prognosis, particularly in Grade 3 oligodendrogliomas.

Vaz-Salgado MA et al. analysed the cyclin pathway, especially p16 expression, in a retrospective cohort of 91 patients diagnosed with oligodendroglioma by the World Health Organization (WHO) 2021 criteria [isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion]. It confirms that the absence of p16 expression is associated with a statistically worse prognosis.

Graphical Abstract