Molecular Aberrations Associated with Seizure Control in Diffuse Astrocytic and Oligodendroglial Tumors

Abstract

Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

Keywords: diffuse astrocytoma; epilepsy; glioma; oligodendroglioma.

Fig. 1.

Microscopic images of tumor specimens stained by immunohistochemistry with different scores. (a) Scoring for Olig2 was defined follows: 0 corresponds to no or rare staining, 1 corresponds to <10% of positively stained cells, 2 to 10–49%, and 3 to ≥50% of positively stained cells, at 200× magnification. (b) Scoring for Ki67 was defined follows: 0 corresponds to <5%, and 1 to ≥5% of positively stained cells, at 200× magnification. (c) Scoring for p53 was defined as follows: 0 corresponds to low (<10%), and 1 to high expression (≥10%) at 200× magnification.

Fig. 2.

Kaplan–Meier estimates of period until the recurrence of seizure. The mean periods until the recurrence of seizure were significantly different between (a) cases with 1p/19q co-deletion and cases without the co-deletion (P = 0.016), and (b) cases with p53 upregulation and cases with normal p53 levels (P = 0.001). There was no significant difference in the mean periods controlled by a single anticonvulsant between (c) cases with tumors positive for ATRX staining and cases with tumors negative for ATRX (P = 0.181).