MBCL-20. MGMT PROTEIN EXPRESSION AND MGMT GENE PROMOTER METHYLATION AS MARKERS OF DRUG SENSITIVITY TO EPIGENETIC THERAPY IN CHILDHOOD MEDULLOBLASTOMA

摘要

The aim of this study was to estimate MGMT protein expression and MGMT gene promoter methylation in medulloblastoma specimens and their prognostic significance. Fifty four patients were treated according to like-SJMB03, MTX-OPEC-based, thiophosphamide/carboplatin-based chemotherapy regimens combined with radiation therapy (average risk group - 22, high risk group - 32). MGMT protein expression and molecular subgroups were assessed by immunohistochemical method. MGMT positive specimen was defined as weak (1+), moderate (2+), strong (3+) colouring of the tumor nuclei and cytoplasm with number of positive tumor cells above 25%. MGMT gene promoter methylation was detected by methylation-specific PCR (MSP) method. MGMT positive tumor cells were revealed in 31 out of (/) 54 specimens (57.4%), 2/10 (20%) - for infants, 29/44 (65.9%) - for children (p = 0.08); MGMT2,3+ - in 13/54 (24%), 0/10 (0%) – for infants, 13/44 (29.5%) – for children (p = 0.049), MGMT gene promoter methylation - in 1/15 (6.7%). MGMT positive endotheliocytes were observed in 25/42 (59.5%). MGMT positive tumor cells and endotheliocytes were revealed in 21/27 (77.8%), in 10/12 (83.3% - for MGMT2,3+). MGMT2,3+ positive tumor cells were detected in 1/12 (8.3% - SHH), 5/12 (41.7% - Group 3), 4/10 (40% - Group 4), p = 0.137. There was not determined any significant correlation between MGMT expression and M0/M+ status, overall survival, event-free survival. These data suggest that the presence of MGMT expression in tumor cells and endotheliocytes opens the way for using demethylating therapeutic agents in patients with Group 3 and Group 4 medulloblastoma.