Expression Of the Idh1 R132h Protein in Hepatopancreatobiliary Malignancies in A Single Center Population: Immunohistochemical Study.

Abstract

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.