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: Xiaoyin Jiang, David A Reardon, Annick Desjardins, James J Vredenburgh, Jennifer A Quinn, Alan D Austin, James E Herndon 2nd, Roger E McLendon, Henry S Friedman
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 114 Issue 1 Pg. 135-40 (Aug 2013) ISSN: 1573-7373 [Electronic] United States
• PMID: 23686298 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• Dacarbazine
• O(6)-Methylguanine-DNA Methyltransferase
• Temozolomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (adverse effects)
• Central Nervous System Neoplasms (drug therapy, metabolism)
• Dacarbazine (adverse effects, analogs & derivatives)
• Drug Resistance, Neoplasm
• Female
• Humans
• Longitudinal Studies
• Lymphoma (drug therapy, metabolism)
• Male
• Middle Aged
• O(6)-Methylguanine-DNA Methyltransferase (metabolism)
• Retrospective Studies
• Temozolomide