O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma |
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Authors: | Xiaoyin Jiang David A Reardon Annick Desjardins James J Vredenburgh Jennifer A Quinn Alan D Austin James E Herndon nd Roger E McLendon Henry S Friedman |
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Institution: | 1. Department of Pathology, Duke University Medical Center, Box 3712 DUMC, Durham, NC, 27710, USA 2. Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215-5450, USA 3. The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, DUMC Box 3624, Durham, NC, 27710, USA 4. Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT, 06105, USA 5. UNC Hospital, 101 Manning Dr, Chapel Hill, NC, 27514, USA
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Abstract: | Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O6-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. |
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