O6-Methylguanine-DNA methyltransferase (MGMT) protein expression in adult anaplastic glioma: relation to tumor and patient characteristics.

A Tortosa MD PhD, M Brell MD, JJ Acebes MD PhD, L Caral MD, JM Gil MD, T Pujol MD, T Ribalta MD PhD, E Verger MD, S Vill, Ã

^aInstitut de Neuropatologia ICS, Bellvitge Hospital, Barcelona, , ^bCiutat Sanitària i Universitària de Bellvitge, Barcelona, , ^cHospital Clínic de Barcelona, Barcelona, , ^dUniversitat de Barcelona, Barcelona

Aim: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from the O6 position of guanine. MGMT activity in glioma cells could be related to resistance to alkylating agents. The aim of this study was to analyze MGMT protein expression in anaplastic gliomas and to establish their relationship among tumour characteristics, patient survival and MGMT protein expression. Methods: Seventy-five patients with anaplastic glioma (anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma WHO III grade) were analyzed for MGMT protein expression by immuno-histochemistry on paraffin-embedded sections. We analyze prognostic implication of patient epidemiological and clinical data (including age, sex, and clinical manifestations at diagnosis), MRI scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative KPS, adjuvant radiotherapy and/or chemotherapy, proliferation index (Ki-67 expression) and MGMT, p53, p16 and EGFR immunohistochemical expression. Results: 50 patients were men and the median age of the patients was 49 years. Forty tumors (42.1%) showed nuclear staining of MGMT and it did not differ significantly among the three astroglial tumor groups. An inverse and statistically significant correlation with age was found (p = 0.02). Conclusion: Although the prognostic value of MGMT expression in gliomas is still controversial, its implication in neurocarcinogenesis and probably in other genetic changes could explain the differences in survival among patients with identical histopathologic diagnosis (anaplastic glioma WHO III grade)

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).