Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma

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.

Keywords: 11C-methionine positron emission tomography; Astrocytoma; CDKN2A/B; IDH-mutant; MTAP.