Abstract

Purpose

The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and ¹¹C-methionine uptake in astrocytomas with IDH mutations.

Methods

We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent ¹¹C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of ¹¹C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis.

Results

Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for ¹¹C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012).

Conclusion

Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of ¹¹C-methionine uptake in astrocytoma, IDH-mutant.

中文翻译：

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IDH 突变型星形细胞瘤中甲硫腺苷磷酸化酶免疫反应性的丧失与不良预后和 11C-蛋氨酸摄取升高相关

摘要

目的

编码甲硫腺苷磷酸化酶的 MTAP 和 CDKN2A/B 在染色体 9q21 上的邻近定位使得 MTAP 表达丧失，作为 CDKN2A/B 纯合删除的替代。本研究旨在确定 MTAP 状态是否与 IDH 突变星形细胞瘤的临床结果和¹¹ C-蛋氨酸摄取相关。

方法

我们对 30 名 IDH 突变型星形细胞瘤患者进行了 MTAP 免疫组织化学分析，这些患者在手术切除前接受了¹¹ C-甲硫氨酸正电子发射断层扫描。使用肿瘤和正常脑组织的平均标准化摄取值(SUV)计算¹¹ C-甲硫氨酸摄取的肿瘤与正常(T/N)比率。 Cox回归分析用于多变量生存分析。

结果

在 IDH 突变型星形细胞瘤中，26.7% (8/30) 表现出细胞质 MTAP 表达缺失，而 73.3% (22/30) 肿瘤保留 MTAP 表达。 MTAP 缺失患者的中位无进展生存期 (PFS) 明显短于 MTAP 保留患者（1.88 年 vs. 6.80 年，p  = 0.003）。 MTAP 缺失患者的中位总生存期 (OS) 也比 MTAP 保留患者短（5.23 年 vs. 10.69 年，p  = 0.019）。多变量分析确定 MTAP 状态（风险比 (HR)，0.081）和切除范围（HR，0.104）作为 PFS 的独立预后因素。缺乏细胞质 MTAP 表达的星形细胞瘤显示¹¹ C-甲硫氨酸摄取的中位 T/N 比显着高于保留 MTAP 的肿瘤（2.12 vs. 1.65，p  = 0.012）。

结论

我们的研究表明，MTAP 表达的缺失与 IDH 突变型星形细胞瘤的不良预后和¹¹ C-蛋氨酸摄取的 T/N 比升高相关。