O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Jiang, X; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Quinn, JA; Austin, AD; Herndon, JE; McLendon, RE; Friedman, HS

Published Date

  • August 2013

Published In

Volume / Issue

  • 114 / 1

Start / End Page

  • 135 - 140

PubMed ID

  • 23686298

Electronic International Standard Serial Number (EISSN)

  • 1573-7373

Digital Object Identifier (DOI)

  • 10.1007/s11060-013-1162-y


  • eng

Conference Location

  • United States