The role of immunohistochemical CIC expression in oligodendrogliomas for recurrence risk stratification

Oligodendrogliomas (ODG) account for ~ 5 - 7% of neuroepithelial tumors. Since the 2016 World Health Organization classification, ODG have been defined by IDH mutation and 1p/19q co-deletion, a genetic profile typically linked with classic oligodendroglial morphology and better survival compared with astrocytic gliomas. Although this genotype is considered a favorable prognostic marker, a subset of ODGs shows early recurrence and aggressive behavior, highlighting the need for additional prognostic indicators. Capicua (CIC), located on chromosome 19q13.2, is a transcriptional repressor downstream of receptor tyrosine kinase signaling. Loss of CIC function increases neural stem cell proliferation, promotes oligodendrocyte progenitor specification, and activates proliferative pathways. Somatic CIC alterations have been reported in up to 70% of ODGs, nearly always in the setting of 1p/19q co-deletion. In this study, we investigated the prognostic value of CIC immunohistochemical (IHC) expression in a homogeneous cohort of IDH-mutant, 1p/19q-codeleted ODGs. Our results demonstrated that complete CIC expression loss and 19q polysomy greater than 22.5%, together with mitotic counts ≥ 6 per 10 high-power fields, were significantly associated with early disease recurrence. Although the absence of molecular confirmation of CIC alterations limits interpretation, the findings suggest that CIC IHC can serve as a surrogate marker to identify patients who may benefit from additional molecular analysis. Conclusion: CIC; loss, 19q polysomy, and elevated mitotic activity may function as valuable prognostic indicators in ODGs. These features could improve risk stratification and guide personalized therapeutic strategies in otherwise favorable cases.