Loss of Heterozygosity and Microsatellite Instability in Diffuse Astrocytic Gliomas: Retrospective Reinterpretation of PCR-Based Molecular Data From a Pre-IDH-Era Korean Cohort.

The 2021 WHO Classification of Tumors of the Central Nervous System incorporates integrated molecular diagnostics into the classification of diffuse gliomas; however, access to comprehensive molecular testing remains limited in some settings. This study retrospectively evaluated grade-associated patterns of PCR-based loss of heterozygosity (LOH) and microsatellite instability (MSI) in a historical, morphology-defined cohort of diffuse astrocytic gliomas from the pre-IDH era. LOH and MSI analyses were performed using 14 LOH and 5 MSI microsatellite markers in 40 archival diffuse astrocytic gliomas, including 12 diffuse astrocytomas, NOS (WHO grade 2), 15 anaplastic astrocytomas, NOS (WHO grade 3), and 13 glioblastomas, NOS (WHO grade 4), collected between 1997 and 2002 prior to the availability of IDH immunohistochemistry. LOH-high (LOH-H) was defined as LOH involving three or more of the seven microsatellite markers examined at each locus, and MSI-high (MSI-H) as instability at two or more of the five markers. LOH was detected in 77.5% of tumors. LOH-H at 10q23 (PTEN) correlated significantly with WHO grade (8.3%, 40.0%, and 61.5% in grades 2, 3, and 4, respectively; p = 0.022) and distinguished high-grade from low-grade tumors (p = 0.015). LOH-H at either 10q23 or 17p13 (TP53) was observed in 67.9% of high-grade tumors compared with 25.0% of grade 2 tumors (p = 0.013). MSI and MSI-H rates were 17.5% and 10.0%, respectively. Three of the four MSI-H tumors lacked concurrent LOH-H; given the small number of MSI-H tumors, this observation is preliminary and should not be interpreted as evidence of distinct genomic instability pathways. LOH-H at 10q23, alone or in combination with 17p13, was associated with higher morphology-based WHO grade, whereas 17p13 LOH alone showed no significant grade association. Because IDH mutation status could not be determined, these findings should not be extrapolated to contemporary WHO-defined astrocytic gliomas; whether these findings apply to molecularly defined gliomas would require validation.