Concordance of Fluorescence <i>In-Situ</i> Hybridization, Whole-Exome Sequencing and Chromosomal Microarray for Evaluating High-Risk Molecular Features in Meningiomas

Abstract Background Meningiomas are the most common primary intracranial tumors, classified into three WHO grades based on histologic and/or molecular criteria. cIMPACT-NOW Update 8 underscores the increasing importance of molecular testing in grading and risk stratification, noting that morphologically WHO grade 1 tumors with concurrent 1p and 22q losses demonstrate clinical behavior comparable to WHO grade 2 meningiomas. This study aimed to assess the concordance of fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) in defining the molecular risk profile of meningiomas. Methods A total of 113 meningiomas were analyzed by WHO grade to assess the concordance of FISH and WES with CMA in detecting CDKN2A homozygous deletion and chromosomal arm losses involving 1p, 10q, 14q, and 22q. Results FISH demonstrated a lower concordance with CMA compared to WES. Some discrepancies likely reflect inherent technical limitations of probe-based assays. Nonetheless, FISH remains widely used as a first-line, and in some settings the only available, method—particularly in resource-limited environments such as low- and middle-income countries. Conclusion Our findings suggest that FISH can provide clinically informative molecular risk assessment in select contexts where more comprehensive platforms are unavailable. However, due to discordance in detecting key copy number alterations, results should be interpreted cautiously. By contrast, CMA and WES offer more reliable alteration detection, making them the preferred platforms for precise molecular risk stratification and prognostication. Refining FISH probe design and establishing optimal thresholds for defining chromosomal arm losses may mitigate some discrepancies, although further validation is needed.