Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system.
Adult grade II low-grade gliomas (LGG) are classified according to the WHO as astrocytomas, oligodendrogliomas or mixed gliomas. TP53 mutations and 1p19q codeletion are the main molecular abnormalities recorded, respectively, in astrocytomas and oligodendrogliomas and in mixed gliomas. Although IDH mutations (IDH1 or IDH2) are recorded in up to 85 % of low-grade gliomas, IDH negative gliomas do occur. We have searched for p53 expression, 1p19q codeletion and IDH status (immunohistochemical detection of the common R132H IDH1 mutation and IDH direct sequencing). Internexin alpha (INA) expression previously recorded to be associated with 1p19q codeletion (1p19q+) gliomas was also analysed. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. In contrast to the WHO classification, this molecular classification predicts overall survival on uni- and multivariate analysis (P = 0.001 and P = 0.007, respectively). Group 4 carries the worst prognosis and group 2 the best. Interestingly, p53 +/INA- expression predicts lack of 1p19q codeletion (specificity 100 %, VPP 100 %). The combined use of these three molecular markers allow for an accurate prediction of survival in LGG. These findings could significantly modify LGG classification and may represent a new tool to guide patient-tailored therapy. Moreover, immunohistochemical detection of p53, INA and mR132H IDH1 expression could represent an interesting prescreening test to be performed before 1p19q codeletion, IDH1 minor mutation and IDH2 mutation detection.
Service d'Anatomie Pathologique et de Neuropathologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France.
Dominique
D
Figarella-Branger
Corinne
C
Bouvier
André Maues
AM
de Paula
Karima
K
Mokhtari
Carole
C
Colin
Anderson
A
Loundou
Olivier
O
Chinot
Philippe
P
Metellus
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014944:World Health Organization
D004273:DNA, Neoplasm; D007381:Intermediate Filament Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C046643:alpha-internexin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human