Prognostic Value of 1p, 19q, 9p, 10q, and EGFR-FISH Analyses in Recurrent Oligodendrogliomas

Abstract

Although 1p/19q codeletions define "genetically favorable" oligodendrogliomas, eventual tumor progression and patient death remain constant. Genetic testing is often performed at the time of recurrence, though it is unclear whether these or other genetic alterations provide useful prognostic information. We characterized 138 of 189 (73%) available primary and recurrent oligodendroglial neoplasms from 80 patients, utilizing paired FISH probes for 1p32/1q42, 19p13/19q13, CEP7/EGFR, CEP9/p16, and PTEN/DMBT1. Patients were followed until death (49%), or a median follow-up of 8.9 years. Patients with 1p/19q codeleted tumors (71%) had an estimated overall median survival of 14.9 years with an estimated 3.9 years from first recurrence. In contrast, those lacking deletions had significantly lower estimated overall median survivals of 4.7 years and 1.0 year after first recurrence (both p < 0.001). This increased survival in patients with 1p/19q codeleted tumors remained significant when adjustments were made for age, tumor grade, type of surgical procedure, and treatment with radiation or chemotherapy. Only 1 recurrence showed focal EGFR amplification, while 5 developed 10q deletions, mostly in high-grade mixed oligoastrocytomas lacking 1p/19q deletions. In contrast, p16 (9p21) deletions were common and associated with both high grade (p < 0.001) and recurrence (p = 0.002). Our data suggest that in classic oligodendrogliomas: 1) 1p/19q tumor status is a powerful predictor of patient survival, even after recurrence; 2) p16 deletions are common progression-associated alterations; and 3) 10q deletions and EGFR amplifications are sufficiently rare to suggest the possibility of alternate diagnoses.

Correlation of in vitro infiltration with glioma histological type in organotypic brain slices

“…An astrocytic (vs oligodendroglial or mixed) phenotype has been found to be highly predictive of shorter TTP in 379 grade II glioma patients (Karim et al, 1996). Up to four times longer TTP was documented for 1p/19q codeleted Ols than for tumours without these deletions (Fallon et al, 2004). Likewise, in a series of pure GBMs and GOCs, 90% of the patients with unusually long TTP had tumours with an oligodendroglial component (Kraus et al, 2000).…”

“…The incidence of 1p/19q loss reported here is in keeping with previous reports on GOCs (Kraus et al, 2001) and 'classic' Ols showing cells with clear halos and typical branching vessels (Sasaki et al, 2002, Watanabe et al, 2002 -11 out of 13 grade II and III Ols and OlAs in this series contained area with these wellrecognised features. 1p/19q codeleted classic Ols are associated with long survival (Fallon et al, 2004) and tend to evolve indolently even without treatment (van den Bent et al, 2003). Although tentatively, we speculate that this particular evolution may be due to limited infiltrative tumour growth.…”

Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma

“…The method to analyze 3p deletion was based on previous studies of deletion of chromosomes 1p and 19q in oligodendrogliomas. 21 The cutoff value for 3p deletion was defined as a 3p/CEP3 ratio of o0.7, as previously described. 11,18,19 …”

Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors

“…6,9 Several of the genetic aberrations in oligodendroglial tumors have been associated with patient outcome. Most importantly, a number of retrospective [10][11][12][13][14][15] as well as recent prospective studies 16,17 have identified 1p/19q deletion as a powerful molecular marker of prolonged survival. Relatively few studies have addressed the prognostic role of other genomic alterations in oligodendroglial tumors.…”