Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma

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Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data regarding the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. A total of 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers were retrospectively analyzed. Clinical, pathological, and survival data were obtained from institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing on paraffin-embedded tissue samples. The median follow-up duration was 3.4 years and the median age at diagnosis was 62 years. IDH1 mutation was identified in 2.3% of cases, while 85.2% were wild-type. Curative surgery was performed for 71.6% of patients and 28.4% received noncurative or palliative treatment. Significant prognostic factors for overall survival included perineural invasion, microvascular invasion, histological subtype, albumin-bilirubin (ALBI) score, surgical margin status, and advanced disease stage. In multivariate analysis, the ALBI score remained independently associated with survival (p = 0.025). The median overall survival was 19.1 months. This study provides the first comprehensive multicenter evaluation of IDH1 mutations and clinicopathological features in iCCA patients. The findings underscore the potential role of molecular profiling in guiding personalized treatment strategies and may serve as a reference for future subtype-specific investigations.

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