article · PubMed
Mutations in the isocitrate dehydrogenase 1 (IDH1) gene represent recognised therapeutic targets across several cancer types. An evaluation of IDH1 R132H protein expression in an Egyptian cohort examined 61 cases of hepatocellular carcinoma, 65 cases of biliary tract cancer, and 29 cases of pancreatic ductal adenocarcinoma using immunohistochemical analysis. High IDH1 expression occurred in 30 per cent of biliary tract cancers, 16.4 per cent of hepatocellular carcinomas, and 6.9 per cent of pancreatic ductal adenocarcinomas, showing lower rates in intrahepatic than extrahepatic cholangiocarcinoma. Elevated expression in hepatocellular carcinoma linked significantly to patients treated with interferon for hepatitis C, notably those without cirrhosis. Furthermore, high expression correlated with lymphovascular invasion in intrahepatic cholangiocarcinoma and the absence of perineural invasion in pancreatic cancer. However, IDH1 status failed to show independent predictive value for overall survival in hepatocellular carcinoma, indicating that it is not a robust prognostic marker.
Understanding the prevalence of targetable cancer alterations across diverse regional populations is critical for evaluating prospective therapies. Although IDH1 mutations represent promising targets for drug development, these findings show that IDH1 R132H expression appears only in specific subsets of liver, biliary, and pancreatic tumours, and cannot be relied upon as an independent marker for patient survival.
This early-stage observational research informs diagnostic developers and oncology trial designers evaluating IDH1-targeted therapies for hepatopancreatobiliary malignancies. Diagnostic screening would be required to stratify the minority of patients expressing the protein. Because IDH1 expression does not independently predict survival outcomes, its direct commercial utility as a standalone prognostic test is limited, placing translation at an early exploratory research stage.
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Background & Objective: Isocitrate dehydrogenase 1 (IDH1) mutations are promising therapeutic targets for various cancers. The study aims to elucidate the frequency of IDH1 expression in hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC), as well as its clinicopathological association in the Egyptian population. Methods: A retrospective cohort comprising 61 HCC, 65 BTC, and 29 PDAC cases was analyzed, with corresponding available control tissues included. IDH1 R132H protein expression was assessed using immunohistochemical analysis. Results: High IDH1 expression was observed in 16.4% of HCC, 30% of BTC, and 6.9% of PDAC, with a lower frequency in intrahepatic compared with extrahepatic cholangiocarcinoma (CC). Elevated IDH1 levels were observed in HCC arising in interferon-treated HCV patients, particularly in the absence of underlying cirrhosis (P = 0.03 and P = 0.002). High IDH1 expression was associated with lymphovascular invasion in iCC and with the absence of perineural invasion in PDAC (P = 0.05 and P = 0.009). IDH1 expression did not emerge as a significant independent predictor of overall survival in the HCC group. Conclusion: High IDH1 expression was observed in subsets of HCC and BTC, and to a lesser extent in PDAC, with no robust prognostic marker in these malignancies. The inconsistent findings regarding IDH1 expression in extrahepatic versus intrahepatic CC may reflect differences in ethnicity, disease etiology, environmental factors, sample size, and methodological approaches.
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DOI: 10.22034/ijp.2026.2085869.3630
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