Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
J Neurooncol. 2013 Aug;114(1):135-40. doi: 10.1007/s11060-013-1162-y. Epub 2013 May 18.
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.
替莫唑胺是一种烷化剂，在治疗原发性中枢神经系统淋巴瘤（PCNSL）方面显示出一定的前景。酶 O(6)-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）可以修复烷化损伤，如替莫唑胺引起的损伤。我们假设 MGMT 免疫组织化学将预测 PCNSL 对替莫唑胺的耐药性。本研究对在我院接受治疗的新诊断和复发性 PCNSL 患者进行了回顾性研究，以研究 MGMT 免疫组织化学对替莫唑胺反应的预测价值。在研究期间，确定了 20 例接受替莫唑胺作为单一药物治疗的患者。6/20 例患者有反应，客观缓解率为 30%（95%CI 8-52）。5 例 MGMT 水平较低（<30%）的患者对替莫唑胺有反应。仅 10 例 MGMT 水平较高（≥30%）的患者中有 1 例对替莫唑胺有反应。由于样本数量小，无法进行正式的统计学比较。2 例完全缓解的患者在替莫唑胺治疗后 6.7 年和 7.2 年仍无疾病进展，存活。免疫组织化学可以对小活检进行检测，以选择性评估肿瘤与周围炎症中的 MGMT 状态。MGMT 免疫组织化学分析可能预测 PCNSL 对替莫唑胺的反应，应进行前瞻性研究。
