P04.22 * OLIGOASTROCYTOMA DOES NOT EXIST: A MOLECULAR GENETIC REAPPRAISAL ON SINGLE-CELL LEVEL

Abstract

Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both, astrocytomas and oligodendrogliomas. We investigated 43 OAs diagnosed in different institutions employing histology, immunohistochemistry and in-situ hybridization addressing surrogates for the molecular genetic markers IDH1R132H mutation, TP53 mutation, ATRX mutation, and 1p/19q co-deletion. In all but one OA the combination of nuclear p53 accumulation and loss of ATRX expression was mutually exclusive of 1p/19q loss. In 31/43 OA only the alterations typical for oligodendroglioma were observed while in 11/43 OA only indicators for mutations associated with astrocytomas were detected. A single case exhibited both, nuclear expression of p53, loss of ATRX expression, IDH1 mutation and 1p/19q loss in all tumor cells. However, this was the only patient undergoing radiotherapy prior to surgery, possibly resulting in acquisition of this uncommon combination. In 30/31 OA with oligodendroglioma typical alterations the portions corresponding to a morphologically astrocytic part were identified to be reactive (i.e. no mutant IDH protein, no p53, ATRX, or 1p/19q aberrations). The remaining case with oligodendroglioma-typical aberrations presented with identical alterations also in the morphologically astrocytic portions. In all 11 OA with astrocytoma-typical alterations the oligodendroglial differentiated areas were neoplastic but harboured identical aberrations as the astrocytic portions. Thus, in this molecular genetic analysis in-situ, none of the 43 diffuse gliomas previously diagnosed as OA revealed separate co-existing cell populations with astrocytoma- and oligodendroglioma-characteristics in the same tumor, despite intra-tumoral heterogeneity in morphology. These data provide strong evidence against the existence of an independent OA entity.