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1p/19q co-deletion is identified in 50–90% of OD/AOD and is especially frequent in tumors bearing a “classic” histology and somewhat less common in anaplastic neoplasms. This genetic abnormality has been also observed in 10–70% of tumors with mixed oligoastrocytic or pure astrocytic morphology, and has been noted, albeit rarely, even in GBM [6, 22, 56, 57].

1p/19q co-deletion is caused by an unbalanced whole-arm translocation between chromosomes 19 and 1, with a total loss of one hybrid chromosome t(1p;19q) and thereby LOH [7, 58, 59]. Genes presumably located at 1p and 19q constitute major targets in current glioma research. Whole-genome sequencing studies have identified inactivating mutations of CIC and FUBP1in 46–83% and 0–31% of OD/AOD, respectively [7, 13, 32, 59, 60]. These genetic alterations have been occasionally observed even in 1p/19q non-codeleted tumors with oligodendroglial morphology, but they are rare in other types of gliomas [7, 32, 60]. Nevertheless, their significance and impact on mechanisms of tumorigenesis currently remain unknown. In general, 1p/19q co-deletion results in proneural gene expression profile [57].

One of the most practical tests used for detection of 1p/19q co-deletion is FISH (fluorescence in situ hybridization) with commercially available fluorescent probes. However, it is effort-dependent and rather expensive. Moreover, false-positive results are often seen because FISH cannot distinguish between partial and complete loss of a chromosomal arm [6, 12, 57, 61]. Microsatellite analysis is a much more reliable technique, but it requires a sample of the patient’s blood. Although at present there are no IHC surrogates for testing of 1p/19q co-deletion, its presence is typically associated with a fairly specific staining pattern. Since this molecular abnormality (as well as mutations of CIC and FUBP1) is tightly associated with IDH1/IDH2 mutations and almost mutually exclusive of TP53 and ATRX mutations, 1p/19q co-deleted tumors are nearly always positive when tested for immunoreactivity to an IDH1^R132H mutation-specific antibody, completely negative for p53, and carry intact ATRX [12, 62]. Vimentin is generally negative, while GFAP and nestin are often positive in oligodendrocytes and minigemistocytes. Additionally, immunopositivity for Class IV intermediate filament alpha-internexin (INA) in WHO grade II gliomas has shown a strong association with 1p/19q co-deletion, providing PPV and NPV of 61 and 77%, respectively [38]. Such an IHC profile in combination with a “classic” histology can be effectively used to define IDH1^R132H-mutant, 1p/19q co-deleted OD/AOD (Fig. 3) [4]. On the other hand tumors without “classic” oligodendroglial morphology may lack 1p/19q co-deletion and harbor either an astrocytoma-like genotype (Fig. 4), or be “triple-negative” [4].

Fig. 3. Oligodendroglioma, IDH1-mutant, 1p/19q co-deleted. Representative tissue section stained with hematoxylin and eosin (H&E) shows round cell nuclei of constant size surrounded by halos, exhibiting a honeycomb or “fried egg” appearance (a). IHC with IDH1^R132H mutation-specific antibody reveals positivity of all neoplastic cells (b). Staining for p53 is completely negative (c). There is retained ATRX expression in the neoplastic cell nuclei (d). FISH using probes against 1p36 and 19q13 shows that cells have a “one orange, two green” signal pattern (e), which is indicative of 1p/19q co-deletion.

Fig. 4. Tumor with morphology of anaplastic oligoastrocytoma, IDH1-mutant, TP53-mutant, 1p/19q non-codeleted. Representative tissue section stained with hematoxylin and eosin (H&E) shows round cell nuclei surrounded by halos, which are intermixed with elongated and multinucleated cells; nuclear atypia is evident (a). IHC with IDH1^R132H mutation-specific antibody reveals positivity of all neoplastic cells (b). Staining for p53 also shows positivity in the majority of nuclei, including round ones (c). Loss of ATRX expression in the tumor cell nuclei is seen (d), while it is preserved (arrow) in the endothelial cells. The Ki-67 positivity (e) is prominent (labeling index 23.1%). FISH did not reveal 1p/19q co-deletion (data not shown). According to the updated WHO classification of CNS tumors (2016) this neoplasm should be classified as “anaplastic astrocytoma.”

Tumors carrying IDH1/IDH2 mutations and 1p/19q co-deletion demonstrate significantly fewer additional genomic alterations, than 1p/19q non-codeleted neoplasms [9]. In LGG 1p/19q co-deletion without IDH1/IDH2 mutation is extremely rare, if it exists at all [12, 22]. While it has been reported that in GBM 1p/19q co-deletion may be independent of IDH1/IDH2 mutational status [37, 57], all tumors with confirmed cytogenetic abnormality, but immunonegative for IDH1^R132H mutation-specific antibody, need to be tested for rare IDH1/IDH2 mutations, which are detectable in many of them [12]. Finally, 1p/19q co-deletion is almost mutually exclusive with HD of CDKN2A, EGFR amplification, and H3 alterations [6, 57].

In cases of OD/AOD 1p/19q co-deletion is widely recognized as a robust prognostic and predictive marker, since it is associated with a universally favorable prognosis and prolonged survival of patients [58, 61], as well as with better tumor response to chemotherapy with procarbazine, CCNU, and vincristine (PCV regimen) [63] and to chemoradiotherapy with TMZ [64]. In the same time, 1p/19q non-codeleted tumors with oligodendroglial morphology demonstrate variable biological behavior [58]. A recent meta-analysis based on 28 studies incorporating 3,408 cases of various gliomas showed statistically significant positive association of 1p/19q co-deletion with progression-free survival (PFS; hazard ratio [HR] 0.63; 95% CI 0.52–0.76) and overall survival (HR 0.43; 95% CI 0.35–0.53) regardless of tumor histopathological type and grade [56]. Mizoguchi et al. [57] reported significantly longer median survival of patients with 1p/19q co-deleted IDH wild-type pGBM (26.6 vs. 12.8 months; p = 0.033). Of note, isolated complete or partial LOH of chromosome 1p is mainly noted in GBM and may be associated with worse prognosis [12, 37]. Partial LOH of chromosome 19q was frequently observed in AA and sGBM, but the clinical significance of this isolated sign is unclear [56, 61].