Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules.

Distinguishing small hepatocellular carcinoma (HCC) from other types of small focal lesions that occur in a cirrhotic liver can be difficult on the basis of morphologic features alone. We investigated whether the expression of glypican-3 (GPC3) could be an ancillary tool in the histopathologic diagnostic process. We performed immunohistochemistry for GPC3 on 16 low-grade dysplastic nodules, 33 high-grade dysplastic nodules, 13 focal nodular hyperplasia-like nodules, and 59 HCCs with a diameter less or equal to 3 cm present in the cirrhotic liver of 66 patients. Both resected lesions and lesions biopsied by needle were included and nonlesional cirrhotic parenchyma was also stained. In a subset of cases (23 samples of cirrhosis, 4 low-grade dysplastic nodules, 5 high-grade dysplastic nodules, 2 focal nodular hyperplasia-like nodules, and 18 HCCs), real time reverse transcriptase-polymerase chain reaction for GPC3 was performed. GPC3 expression was, both on immunohistochemistry and by real time reverse transcriptase-polymerase chain reaction, much higher in small HCCs than in cirrhosis and other types of small focal lesions, indicating that the transition from premalignant lesions to small HCC is associated with a sharp increase of GPC3 expression in a majority of cases. The sensitivity and specificity of a positive GPC3-staining for the diagnosis of HCC in small focal lesions was 0.77 and 0.96, respectively, in resected cases, and 0.83 and 1, respectively, for needle biopsies. Because the result of the staining was easily interpretable, immunohistochemistry for GPC3 is valuable ancillary tool in the histopathologic diagnosis of small focal lesions in cirrhosis.