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

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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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Acknowledgments

The authors would like to acknowledge Ms. Debra Fleming and Mrs. Kathryn Perkinson for their technical assistance.

Ethical standards

The described experiments comply with the current laws of the United States.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Duke University Medical Center, Box 3712 DUMC, Durham, NC, 27710, USA

    Xiaoyin Jiang, Alan D. Austin & Roger E. McLendon

  2. Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215-5450, USA

    David A. Reardon

  3. The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, DUMC Box 3624, Durham, NC, 27710, USA

    Annick Desjardins, James E. Herndon 2nd & Henry S. Friedman

  4. Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT, 06105, USA

    James J. Vredenburgh

  5. UNC Hospital, 101 Manning Dr, Chapel Hill, NC, 27514, USA

    Jennifer A. Quinn

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  1. Xiaoyin Jiang
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Correspondence to Xiaoyin Jiang.

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Jiang, X., Reardon, D.A., Desjardins, A. et al. O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma. J Neurooncol 114, 135–140 (2013). https://doi.org/10.1007/s11060-013-1162-y

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  • DOI: https://doi.org/10.1007/s11060-013-1162-y

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