Impact of 9p deletion and p16, Cyclin D1, and Myc hyperexpression on the outcome of anaplastic oligodendrogliomas

Abstract

ObjectiveTo study the presence of 9p deletion and p16, cyclin D1 and Myc expression and their respective diagnostic and prognostic interest in oligodendrogliomas.MethodsWe analyzed a retrospective series of 40 consecutive anaplastic oligodendrogliomas (OIII) from a single institution and compared them to a control series of 10 low grade oligodendrogliomas (OII). Automated FISH analysis of chromosome 9p status and immunohistochemistry for p16, cyclin D1 and Myc was performed for all cases and correlated with clinical and histological data, event free survival (EFS) and overall survival (OS).ResultsChromosome 9p deletion was observed in 55% of OIII (22/40) but not in OII. Deletion was highly correlated to EFS (median = 29 versus 53 months, p<0.0001) and OS (median = 48 versus 83 months, p<0.0001) in both the total cohort and the OIII population. In 9p non-deleted oligodendrogliomas, p16 hyperexpression correlated with a shorter OS (p = 0.02 in OII and p = 0.0001 in OIII) whereas lack of p16 expression was correlated to a shorter EFS and OS in 9p deleted OIII (p = 0.001 and p = 0.0002 respectively). Expression of Cyclin D1 was significantly higher in OIII (median expression 45% versus 14% for OII, p = 0.0006) and was correlated with MIB-1 expression (p<0.0001), vascular proliferation (p = 0.002), tumor necrosis (p = 0.04) and a shorter EFS in the total cohort (p = 0.05). Hyperexpression of Myc was correlated to grade (median expression 27% in OII versus 35% in OIII, p = 0.03), and to a shorter EFS in 9p non-deleted OIII (p = 0.01).ConclusionChromosome 9p deletion identifies a subset of OIII with significantly worse prognosis. The combination of 9p status and p16 expression level identifies two distinct OIII populations with divergent prognosis. Hyperexpression of Bcl1 and Myc appears highly linked to anaplasia but the prognostic value is unclear and should be investigated further.

Cutaneous pilomatrical carcinosarcoma: a case report with molecular analysis and literature review

“…The association of p16 overexpression and deletion of the p16 gene (CDKN2a, 9p21) with high grade histology and unfavorable prognosis have been recently reported in various cancers [19][20][21][22][23][24]. In the present case, immunohistochemical analysis demonstrated overexpression of p16 in both components of the tumor (Fig.…”

Oligodendroglioma: A Review of Management and Pathways

“…Interestingly, some tumors exhibited p16 hyperexpression without any chromosome 9p alterations and this was associated with a shorter EFS and OS. Cyclin D1 expression was also significantly higher in AO and was associated with a shorter EFS (Michaud et al, 2018).…”

“…While often found upregulated in many tumors, FUBP1 acts as a tumor suppressor gene due to its inactivating mutations reported in around 15% of oligodendroglial tumors (Baumgarten et al, 2014). As for the clinical relevance of these molecular markers, inactivating mutations affecting FUBP1 have correlated with a shorter time to recurrence and CIC mutations have been associated with worse prognosis, especially in those patients with 1p/19q co-deleted oligodendrogliomas (Chan et al, 2014;Michaud et al, 2018). Nevertheless, further studies are needed to elucidate the role of CIC/FUBP1 alterations in the pathogenesis of AO and oligodendrogliomas, in general.…”

“…In addition to the aforementioned pathways, homozygous and the less common hemizygous losses of 9p21 have been reported with high frequencies in gliomas, and up to 55% in AO (Maruno et al, 1996;Perry et al, 1999;Rasheed et al, 2002;Ohgaki and Kleihues, 2009;Michaud et al, 2018). These alterations have correlated with a shorter event free survival (EFS; 29 vs. 53 months, p < 0.0001) and OS (48 vs. 83 months, p < 0.0001).…”