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

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) <i>P</i> = 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 (<i>P</i> = 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.