OBJECTIVE: Diagnosis of metastatic liver carcinomas (MLCs) vs. hepatocellular carcinomas (HCCs) may be problematic especially in the non-cirrhotic liver. Glutamine Synthetase (GS), Glypican3 (GPC3, and Arginase-1 (Arg-1) immunohistochemistry can demonstrate the hepatocellular origin of a given tumor. This study aims to investigate the characteristics of GS, GPC3, and Arg-1 expression and the value of their combination in MLCs and in HCCs.
PATIENTS AND METHODS: Tissue samples were obtained from 86 patients with liver tumors, (16 HCCs, 70 MLCs) who underwent liver transplantation or resection. Immunohistochemical staining for GS, GPC3, and Arg-1 was performed on formalin fixed paraffin embedded sections. Demographic, laboratory, and clinical data obtained from patient files were analyzed for the confirmation of the primary origin of the tumors. Statistical analyses were made using the SPSS version 19.0 (IBM, Armonk, NY, USA).
RESULTS: Staining pattern of GS and GPC3 was cytoplasmic. Arg-1 staining was cytoplasmic in MLCs vs. cytoplasmic and nuclear in HCCs. Among HCCs, 100%, 38%, and 94% showed positive staining with GS, GPC3, and Arg-1, respectively. Overall, MLCs showed positive staining with GS, GPC3, and Arg-1 in 73%, 4%, and 4% of the cases, respectively. The combination of GS+/GPC3+/Arg-1+ was detectable in 38% of HCCs, but in 0% of MCTs. The specificity of GS, GPC3, and Arg-1 for HCC was 27%, 96%, 96%, and sensitivity was 100%, 38%, and 94%, respectively.
CONCLUSIONS: Expression of GS in MLCs is high, therefore GS/GPC3/Arg-1 should be used as a panel in addition to other markers when the differential diagnosis of MLC vs HCC is challenging. Cytoplasmic and nuclear Arg-1positivity should be a prerequisite for the diagnosis of HCC.