OS5.4 Not all 1p/19q non-codeleted oligodendroglial-like tumors are astrocytic

摘要

Although combined chromosomal 1p and 19q deletion is the genetic hallmark defining oligodendrogliomas, approximately 30% to 40% of oligodendroglial tumors have intact 1p/19q as shown in most international series and demonstrate aggressive clinical course. This group of 1p/19q intact oligodendroglial tumors is frequently suggested to be derived from astrocytic lineage and remains as an under-investigated entity. In the present study, we provided evidence that not all 1p/19q intact oligodendroglial tumors are of astrocytic lineage through histologic and molecular approaches. We examined 1p/19q status by interphase fluorescence in-situ hybridization in a large cohort of 337 oligodendroglial tumors collected from Prince of Wales Hospital (Hong Kong) and Huashan Hospital (Shanghai), and identified 134 cases (39.8%) lacking 1p/19q codeletion which was independently associated with poor prognosis across the cohort by multivariate analysis. Among this 1p/19q intact oligodendroglial tumor cohort, 58 cases (43.3%) demonstrated classic oligodendroglial histology which showed older patient age (p=0.01), better prognosis (p<0.000001), association with grade III histology (p=0.009), PDGFRA expression (p=0.019), TERTp mutation (p=0.007), as well as frequent IDH mutation. More than half of the 1p/19q intact oligodendroglial tumors showed lack of astrocytic defining markers, p53 immunoexpression and ATRX loss, indicating their non-astrocytic phenotype molecularly. TP53 mutational analysis was additionally conducted in a subset (45 cases) of the 1p/19q intact oligodendroglial tumors. Wild-type TP53 was detected in 32 cases (71.1%) which was associated with classic oligodendroglial histology (p=0.045). Importantly, IDH and TERTp co-occurred in 75% of 1p/19q intact, TP53 wild-type oligodendrogliomas (p=0.012), highlighting the potential of the co-mutation in assisting diagnosis of oligodendroglioma in tumor with clear cell morphology and non-codeleted 1p/19q status. In summary, our study demonstrated that not all 1p/19q intact oligodendroglial tumors are astrocytic and co-evaluation of IDH and TERTp mutation could potentially serve as an adjunct for diagnosing 1p/19q intact oligodendroglioma.