Ni-1 Methylthioadenosine Phospholylase Status Correlates With Prognosis and Methionine Uptake in Idh Mutant Astrocytoma

Abstract

Purpose Methylthioadenosine phosphorylase (MTAP) immunohistochemistry staining has been proposed as a surrogate of Cyclin-dependent kinase inhibitor 2A homozygous deletion (CDKN2A HD) in various type of tumors. This study was designed to determine whether MTAP status correlates with clinical outcome and uptake of 11C-methionine in astrocytoma with IDH mutations. Methods We conducted a MTAP immunohistochemistry staining of 30 IDH-mutant astrocytoma patients who underwent 11C-methionine positron emission tomography scans prior to surgical resection from 2000 to 2020. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. Results Eight of the thirty astrocytomas harboring IDH mutations exhibited loss of cytoplasmic MTAP expression, which is accompanied with a poor prognosis. The median progression free survival (PFS) in IDH-mutant astrocytoma patients with loss of MTAP was 1.88 years, significantly shorter than that of those with MTAP retention (6.80 years, p=0.003). The median Overall survival (OS) in IDH-mutant astrocytoma patients with loss of MTAP was 5.23 years, again significantly shorter than that of those with MTAP retention (p=0.0191). Multivariate analysis revealed MTAP status to be an independent prognostic marker for PFS in IDH-mutant astrocytoma patients. The median T/N ratio in tumors with loss of cytoplasmic MTAP expression was 2.12 (IQR 1.92-2.50), i.e., significantly higher than that of tumors with MTAP retention (1.65, IQR 1.23-1.94, p=0.0116, U test). Conclusion Our study showed MTAP status to correlate with clinical outcome and T/N ratio of astrocytoma patients with IDH mutations.