Current Diagnosis and Treatment of Oligodendroglioma

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Neurosurg Focus. 2002;12(2) 

In This Article

Clinical Prognostic Factors and Survival

In addition to the aforementioned resection-and histology-related aspects, other prognostic factors have been reported for oligodendroglial tumors. Age has been found to be one of the strongest independent predictors of survival.[35,71,74,92] Older age is associated with more aggressive tumor behavior and a worse prognosis, whereas in patients younger than age 40 to 45 years a significantly longer survival time has been documented.[9,12,45,58,63,71,74,93] The presence of a neurological deficit at the time of diagnosis has also been reported to predict a poor outcome.[9,12,22,91,92] In patients with low-grade oligodendrogliomas who present clinically with seizures and have no neurological deficits, a significantly better outcome has been reported than in those with raised intracranial pressure or neurological deficits.[9,12,34]

Other favorable features include location in the frontal lobe (which may relate to the extent of resection possible) and higher initial or postoperative functional performance status.[1,22,45,71] Additional studies are currently underway in which the authors may be able to confirm the validity of these clinical prognostic factors (H Engelhard, et al., unpublished data).

The survival times reported in recent studies are already significantly longer than those cited only a few years ago. In 2001 Henderson and Shaw[38] reported 5- and 10-year survival rates of 73% and 49%, respectively, for patients with Grade II oligodendroglioma. In 2000 Olson, et al.,[58] reported a median survival time of 16.7 years in their series of patients with oligodendroglioma and mixed glioma. The authors of other studies have published similar results.[2,34,48,63,68] Despite the information available, it is difficult to predict survival for the individual oligodendroglioma patient on clinical grounds, given the following factors: 1) earlier diagnosis and improved surveillance provided by MR imaging; 2) rapid evolution in treatment taking place; and 3) possibility of conversion to an anaplastic tumor that is refractory to all treatments.[31,50]

Molecular Biology and Tumor Markers. Significant advances have recently been made in our understanding the molecular genetics of oligodendroglioma. Oligodendrogliomas generally demonstrate distinct genetic alterations that distinguish them from other types of gliomas. Their most frequent genetic alteration is the LOH on the long arm (designated "q") of chromosome 19. In published studies, the incidence of LOH on 19q has varied from 50 to more than 80% of cases.[4,41,65,77,89] The second most frequent genetic alteration is LOH on the short arm (designated "p") of chromosome 1. The incidence of LOH on 1p has been reported to range from 40 to 92%.[5,65,77] Such molecular markers have now been shown to have prognostic value in cases of oligodendrogliomas. Specifically, LOH on chromosome arm 1p (especially if accompanied by loss on 19q) appears to be strongly associated with the oligodendroglial phenotype and also an independent predictor of response to chemotherapy (with or without radiotherapy) and survival, in cases of high-and low-grade oligodendrogliomas.[3,11,39,77,83] Ino, et al.,[39] however, have recently reported that the loss of 1p does not identify all the chemosensitive tumors, nor was long survival demonstrated in all the patients with 1p loss. Therefore, further clarification of these findings is needed.

Cell proliferation markers such as Ki-67 and proliferative cell nuclear antigen have been studied in oligodendrogliomas to provide additional information regarding tumor behavior.[63] The Ki-67 antigen is recognized by the MIB-1 antibody. Typically, in WHO Grade II oligodendrogliomas, because mitotic activity is absent, labeling indices for proliferation markers such as Ki-67 are quite low. In some studies, Ki-67 staining has been reported to have prognostic significance (with higher staining implying poorer prognosis) and also to be higher in recurrent tumors than in the original tumors.[17,44,63,66] Increased proliferative activity assessed by flow cytometry (as indicated by a higher percentage of cells in the S phase) has also been strongly associated with decreased survival time.[16]

Enzyme markers have also been studied in oligodendroglioma. In a recent study, in which topoisomerase II- (a molecular target for cytotoxic drugs) was evaluated, the authors found that it is associated with a higher proliferation rate and a poorer prognosis in patients with oligodendrogliomas. Topoisomerase was therefore suggested to be a useful marker for the selection of oligodendroglioma patients in whom a poorer prognosis exists and who would therefore be candidates for earlier adjuvant therapy.[53] In another new immunohistochemical study, investigators evaluated the COX isoenzymes, COX-1 and COX-2.[25] The COX-1 enzyme is expressed in macrophages/microglial cells. Patients with low COX-1 labeling scores were found to have a better survival than those with high scores. Because COX-2-expressing astrocytes were found to be present around areas of tumor necrosis, its expression was found to be significantly lower in the more benign oligodendrogliomas than in higher-grade oligodendrogliomas.

Uncommonly in oligodendrogliomas, there is decreased expression of the cell-cycle regulatory protein p16, which is encoded by a gene designated CDKN2A. If a CDKN2A deletion (or a decrease in p16 expression) does occur, it may be an important negative prognostic indicator.[7,11,54,69]

The p53 protein, nicknamed "the guardian of the genome," has also been studied in oligodendrogliomas. Oligodendrogliomas have demonstrated p53 gene mutations in a small subset of cases.[43,59] Growth factors that have been studied include vascular endothelial growth factor, the epidermal growth factor receptor, and platelet-derived growth factor. The expression of vascular endothelial growth factor in oligodendroglioma has been evaluated as a possible prognostic factor, and results have been mixed.[42] Epidermal growth factor receptor does seem to be expressed in these tumors regardless of prognosis.[66,76] Platelet-derived growth factors A and B and their receptors have also been found to be consistently expressed.[28,67] Loss of the p18 tumor suppressor gene, which is located on chromosome 1p, may be involved in the progression of oligodendrogliomas.[37]

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