CLINICAL utility of assessing CDKN2A status in recurrent astrocytomas

Abstract

IDH-mutant astrocytomas exhibit a more indolent natural history and better prognosis compared to their IDH-wild type counterparts. WHO 2021 classification integrated CDKN2A/B homozygous deletion as a crucial criterion for grading these tumors, emphasizing its prognostic implications. FISH assay is commonly used to assess CDKN2A status, but guidelines for interpreting FISH results for glioma prognostication are not well-defined in the literature. We conducted an ambispective study involving 22 cases of recurrent IDH-mutant astrocytomas, including primary tumor samples. Histopathological assessments, including WHO grading and molecular profiling, were performed. Immunohistochemistry confirmed IDH mutation status, and FISH analysis evaluated CDKN2A homozygous deletion. Homozygous CDKN2A deletion was detected in only 1/22 (4.8%) of primary tumors, which was grade 3 astrocytoma, and significantly more frequent in recurrent cases, particularly in histological grade 2/3 tumors (35.3%). Patients harboring CDKN2A deletions exhibited significantly poorer overall survival, highlighting its prognostic significance. Our findings highlight the clinical relevance of CDKN2A assessment in recurrent IDH-mutant astrocytomas and its utility as a prognostic marker. We propose a selective approach to FISH testing, focusing on primary grade 3 and all recurrent cases, regardless of histology grade, to optimize diagnostic accuracy and stratification for personalized treatment strategies.