IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by pyrosequencing.

Background: Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma (iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically, poor differentiation and clear cell change are associated with IDH1 mutation in iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC, some specific subtypes of HCC might show a higher IDH1 mutation rate than reported before (0.5-1.5%).

Methods: Forty-six cases of iCC and 48 cases of HCC (including 20 cases of clear cell type and 13 cases of pseudoglandular pattern) were tested for IDH1 mutation by pyrosequencing.

Results: Three cases in iCC (6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation rate between iCC and HCC demonstrated no significant difference, clear cell HCC revealed statistically increased mutation rate compared to that of HCC without clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor survival in clear cell HCC patients (P = 0.004).

Conclusions: Clear cell HCC showed higher frequency of IDH1 mutation rate than other variants of HCC. This result consolidates the assumption that morphological features of tumors reflect molecular alterations.