gms | German Medical Science

The combined loss of chromosomes 1p-19q has recently emerged as a genetic predictor of chemo sensitivity in oligodendroglioma. This has been the first demonstration of the therapeutic usefulness of the genotyping of brain neoplasm. The notion that gene-expression subgroups could represent distinct type of disease has leaded us to relate gene-expression data of oligodendroglioma and their clinical and / or biological behaviour.

The surgical pathology files, of the Rennes University Hospital, were searched for cases in which a diagnosis of oligodendroglioma was made. Cases between 1990 and 2002 were selected. Over 145 newly diagnosed oligodendrogliomas, 87 patients with pure supratentorial oligodendroglioma (astrocytic component of less than about 20% of the total cells) were selected. Allelic loss of chromosome 1p-19q was evaluated by fluorescence in situ hybridization (FISH) of formaline-fixed, paraffin-embedded tissue. The end-point of follow up for the study was January 2004.

Parameters evaluated included clinical data (age, sex, onset, clinical examination, symptoms duration, location), radiological (contrast enhancement), and histological features (necrosis, vascular proliferation, mitosis, cell density, p18, p27, MiB1, VEGF). Univariate and multivariate analysis was computed with available software (SPSS^© 12.0 for Windows; SPSS, Inc., Chicago, IL). Correlations of categorical variables were investigated using the Pearson correlation test. Comparison between survival curves was done using univariate Cox's regression analysis. Cox regression analysis was performed using the Wald criteria and both ascending and descending procedures; p value less than 0.05 (P<0.05) considered as statistically significant.

The 87 patients included 48 women (55%) and 39men (45%) (p=0.0025). Overall mean age at presentation is 45±16years (range 11-73 years) for women and 36±13 years (range 5-67 years) for men (p=0.006).

All patients underwent total or subtotal excision with adjuvant radio-chemotherapy in 36 cases (41%), radiotherapy in 29 cases (33%), and in 21 patients (24%), only surgery was performed. Univariate analysis disclosed as prognostic factors: younger age (p=10^-5), female (p=0.0025), seizure as presenting symptom (p=10^-5), normal clinical examination (p=10^-5), lack of radiological enhancement (p=0.0231), lack of histological necrosis (p=0.0003), no mitoses (p=0.0014), 1p-19q deletion (0.0001), no recurrence (p=0.0021), and adjuvant radio-chemotherapy (p=10^-5). Multivariate analysis resorted that only age (P<10^-5) (OR: 1.026; IC 95%: 1.049; 1.074) and chromosomal anomalies (p<0.002) (OR: 3.5; IC 95%: 4.3; 9.2) for no 1p-19q deletion group and (OR: 7.4; IC 95%: 3.0; 13.7) for polysomia subtype with 1p -19q deleted oligodendroglioma as a reference group) are independently linked with survival. On the other hand, in addition to 1p-19q deleted-oligodendroglioma (mean survival period 130 months) two molecular subtypes of oligodendroglioma have emerged:

• Oligodendrogliomas showing polysomia, which have lack of meaningful responses to both radio and chemotherapy with a particular ominous prognosis (mean and median survival period of 51-34 months) and a high rate of recurrence (74%)

• Oligodendrogliomas with no 1p-19q deletion (mean survival period 83 months), which have an intermediate path between the firsts, cited molecular subtypes.

According to our data, oligodendrogliomas could be subdivided in three molecular subtypes:

• Oligodendrogliomas showing 1p-19q deletion

• Oligodendrogliomas with no 1p-19q deletion

• Oligodendrogliomas with polysomia Up to now, the literature has presented conflicting views regarding both the influence on survival of individual pathological features and the management of oligodendroglioma. Molecular data, to a certain extent, may explain this correlation heterogeneity between histological features and prognosis. Furthermore, molecular genetic assay has provided a hypothesis for developing rational treatment strategies, although this does not mean death of traditional histopathology, which will not lose its importance. Pathological confirmation is mandatory, while its interpretation will be enhanced by molecular genetic as it was by immuno-histochemistry.