Survival analysis of presumptive prognostic markers among oligodendrogliomas

• Published in: Cancer 2005-10, Vol.104 (8), p.1693-1699
• Main Authors: McLendon, Roger E., Herndon, James E., West, Bryan, Reardon, David, Wiltshire, Rodney, Rasheed, B. K. Ahmed, Quinn, Jennifer, Friedman, Henry S., Friedman, Allan H., Bigner, Darell D.
• Format: Article
• Language: English
• Subjects: 19q; 9p21; Biological and medical sciences; Biomarkers, Tumor - analysis; Brain Neoplasms - chemistry; Brain Neoplasms - mortality; Chromosomes, Human - genetics; Cohort Studies; Disease-Free Survival; fluorescence in situ hybridization; genetic testing; Humans; In Situ Hybridization; Loss of Heterozygosity; Medical sciences; methylguanine methyltransferase; Neoplasm Proteins; Neurology; O-Methylguanine-DNA Methyltransferase - analysis; oligodendroglioma; Oligodendroglioma - chemistry; Oligodendroglioma - mortality; Prognosis; Retrospective Studies; Survival Rate; TP53; Tumor Suppressor Protein p53 - analysis; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21362

BACKGROUND Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of oligodendroglial tumors and represents a possible mechanism for this therapeutic sensitivity. However, the authors questioned the relevance of genetic testing and measuring MGMT levels in tumors that were diagnostic of oligodendroglioma. METHODS The authors performed a retrospective analysis of 1p, 19q, 9p21, TP53, and MGMT status in 46 patients with oligodendrogliomas to address any relations that may exist among these markers with regard to progression‐free survival (PFS) and total survival. Methodologies included comparative genomic hybridization; loss of heterozygosity (LOH) on 1p, 19q, and 9p21; TP53 mutational analysis; and immunohistochemistry for MGMT. RESULTS The authors found that survival among patients with light microscopically diagnosed oligodendroglial tumors demonstrating LOH of 1p and 19q trended toward statistical significance (P = 0.102 and P = 0.058, respectively). 9p21 LOH was significant as a predictor of PFS only among anaplastic oligodendrogliomas in this cohort (P = 0.033). TP53 mutation was found to be significantly predictive of a shorter survival (P = 0.027) among all patients and exhibited a strong trend toward a shorter PFS (P = 0.060). Low‐level MGMT labeling index (LI) (< 20%) was noted in 86% of all oligodendroglial tumors. MGMT LI was not found to correlate with an improved PFS or total survival in this cohort, recognizing that median survival was not reached after a median follow‐up of 104 months. CONCLUSIONS 9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas. Cancer 2005. © 2005 American Cancer Society. Among tumors diagnosed as oligodendrogliomas by light microscopy, loss of heterozygosity of 9p21 and TP53 mutational analysis revealed prognostically useful information. Only 14% of these tumors exhibited high methylguanine methyltransferase (MGMT) levels, a rate that is significantly less than that noted in astrocytomas, yet among these oligodendrogliomas, the MGMT expression patterns were found to be independent of 1p and 19q status.