title: O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma.
abstract: Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8-52). Five patients with low MGMT level (<30 %) showed a response to temozolomide. Only one of 10 patients (10 %) with high MGMT level (≥30 %) exhibited a response to temozolomide. Small sample numbers precluded formal statistical comparisons. Two patients with complete response remain alive without progressive disease 6.7 and 7.2 years after temozolomide initiation. Immunohistochemistry can be performed on small biopsies to selectively assess MGMT status in tumor versus surrounding inflammation. MGMT analysis by immunohistochemistry may predict response to temozolomide in PCNSL and should be prospectively investigated.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. jiang009@mc.duke.edu
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Jiang
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Quinn
authors.forename: Alan D
authors.initials: AD
authors.lastname: Austin
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D012189:Retrospective Studies; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide