SOMATIC DEFICIENT MISMATCH REPAIR ASSESSED BY IMMUNOHISTOCHEMISTRY AND CLINICAL FEATURES IN BRAZILIAN GLIOBLASTOMA PATIENTS.

C A F Yamada, S M F Malheiros, L L F Do Amaral, C L P Lancellotti
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Abstract

Background: Glioblastoma (GBM) is the most frequent primary malignant CNS tumor. Deficient mismatch repair (dMMR) is associated with better prognosis and is a biomarker for immunotherapy. Evaluation of MMR by immunohistochemistry (IHC) is accessible, cost effective, sensitive, and specific.

Aim: Our objective was to investigate MMR proteins in adult GBM patients.

Materials and methods: We retrospectively analyzed 68 GBM samples to evaluate the proficiency of MMR genes expression assessed by IHC. Clinicopathologic and molecular features were compared in proficient (pMMR) or dMMR.

Results: 10 (14.7%) samples showed dMMR, and the most frequent was MSH6 (100%) followed by MSH2, PMS2, and MLH1. We observed heterogeneous expression of dMMR in 5 GBMs. The median overall survival did not differ between pMMR (19.8 months; 0.2-30) and dMMR (16.9 months; 6.4-27.5) (p = 0.31). We observed a significantly higher overall survival associated with gross total resection compared to subtotal resection or biopsy (30.7 vs. 13.6 months, p = 0.02) and MGMT methylated status (29.6 vs. 19.8 months, p = 0.049). At the analysis time, 10 patients were still alive, all in the pMMR group.

Conclusions: Our data demonstrated dMMR phenotype assessed by IHC in an expressive portion of GBM patients, however without significant impact on overall survival.

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通过免疫组化和临床特征评估巴西胶质母细胞瘤患者的体细胞错配修复缺陷。
背景:胶质母细胞瘤(GBM)是最常见的原发性中枢神经系统恶性肿瘤。错配修复缺陷(dMMR)与较好的预后有关,是免疫疗法的生物标志物。通过免疫组化(IHC)评估MMR是一种方便、经济、灵敏和特异的方法:我们回顾性分析了 68 例 GBM 样本,以评估 IHC 评估 MMR 基因表达的准确性。结果:10 例(14.7%)样本中的 MMR 基因表达为 "pMMR",而 "dMMR "样本中的 MMR 基因表达为 "dMMR":结果:10 个样本(14.7%)出现了 dMMR,其中最常见的是 MSH6(100%),其次是 MSH2、PMS2 和 MLH1。我们在5个GBM中观察到dMMR的异质性表达。pMMR(19.8 个月;0.2-30)和 dMMR(16.9 个月;6.4-27.5)的中位总生存期没有差异(p = 0.31)。我们观察到,与次全切除术或活检相比,全切除术的总生存期(30.7 个月 vs. 13.6 个月,p = 0.02)和 MGMT 甲基化状态(29.6 个月 vs. 19.8 个月,p = 0.049)明显更高。截至分析时间,仍有10名患者存活,全部属于pMMR组:我们的数据表明,IHC评估的dMMR表型在一部分GBM患者中具有表现力,但对总生存期没有显著影响。
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