NIMG-65. METHYLTHIOADENOSINE PHOSPHORYLASE STATUS CORRELATES WITH CLINICAL OUTCOME AND11C-METHIONINE UPTAKE IN ASTROCYTOMA, IDH-MUTANT

Abstract

Abstract PURPOSE Methylthioadenosine phosphorylase (MTAP) immuno histochemistry staining has been proposed as a surrogate of Cyclin-dependent kinase inhibitor 2A homozygous deletion (CDKN2A HD) in various types of tumors. This study was designed to determine whether MTAP status correlates with clinical outcome and uptake of 11C-methionine in astrocytoma, IDH-mutant. METHODS We conducted a MTAP immunohistochemistry staining of 30 astrocytoma, IDH-mutant patients who underwent 11C-methionine positron emission tomography scans prior to surgical resection from 2000 to 2020. The tumor-to-normal (T/N) ratio 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 (26.7%) of the thirty astrocytoma, IDH-mutant patients exhibited loss of cytoplasmic MTAP expression, which is accompanied with a poor prognosis. The median progression free survival (PFS) in astrocytoma, IDH-mutant patients with loss of MTAP was 1.88 years and significantly shorter than that of those with MTAP retention (6.80 years, p = 0.003). The median Overall survival in astrocytoma, IDH-mutant patients with loss of MTAP was 5.23 years, again significantly shorter than that of those with MTAP retention (10.69 years, p = 0.0191). Multivariate analysis revealed that MTAP status was an independent prognostic marker for PFS in astrocytoma, IDH-mutant 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). Thirteen (59.1%) of twenty-two patients with MTAP retention recurred and nine patients underwent a second surgery after radiation treatment with or without chemotherapy. Three (33.3%) of the nine recurrent patients showed loss of MTAP immunoreactivity, suggesting a role for this loss in tumor progression. CONCLUSION Our study showed MTAP status to correlate with clinical outcome and T/N ratio of 11C-methionine in astrocytoma, IDH-mutant patients.