Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma

Abstract

Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic.We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma.

Is It Worth Considering Multicentric High-Grade Glioma a Surgical Disease? Analysis of Our Clinical Experience and Literature Review

“…In fact, according to the few studies analyzing molecular patterns of these entities, the former appeared to have an IDHwt tumorigenesis. This last data would suggest the absence of a low-grade progenitor and, as a consequence, an evolutive pattern would not seem probable [12]. Anyway, Sridharan…”

“…In fact, according to the few studies analyzing molecular patterns of these entities, the former appeared to have an IDHwt tumorigenesis. This last data would suggest the absence of a low-grade progenitor and, as a consequence, an evolutive pattern would not seem probable [12]. Anyway, Sridharan et al described two cases of LGG in the same patient without an apparent pattern of diffusion, making fall this condition into the concept of multicentricity [13].…”

Simultaneous Supratentorial and Infratentorial Pilocytic Astrocytomas in an Adult Patient with Concurrent Neurofibromatosis Type 1 and HIV Infection

“…In a genetic analysis of 14 patients with multicentric gliomas, although only 4 were classified as low-grade, all were consistently negative for mutant IDH1, suggesting that multicentric gliomas exhibit characteristics related to their mutant IDH1 negativity that differ from those of mutant IDH1 gliomas. 27 In addition, IDH1/2 wild-type status is recognized to be associated with worse prognosis in patients with gliomas. 28 Several factors have been identified as prognostic for CNS tumors in patients with NF1.…”

The many faces of glioblastoma: Pictorial review of atypical imaging features

“…This suggests that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. 25…”