Expression of liver fatty acid binding protein in hepatocellular carcinoma

Abstract

Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors.

Keywords: HNF1A; Hepatocellular adenoma; Hepatocellular carcinoma; Liver fatty acid binding protein; Well differentiated hepatocellular neoplasm.

Fig. 1

Case 1: Well-differentiated hepatocellular carcinoma (HCC) arising in HNF1A-inactivated variant hepatocellular adenoma (HCA). A, The right-hand portion of each panel shows the HNF1A-inactivated HCA portion of the tumor, whereas the left-hand portion of each panel shows the HCC portion of the tumor, hematoxylin and eosin, original magnification ×200. B, Loss of staining for reticulin is seen in the HCC component (left), ×200. C, Complete loss of staining for LFABP is seen in both components, compared to the intact staining seen in the background uninvolved liver parenchyma (inset), ×200.

Fig. 2

Spectrum of LFABP staining. A, Case 4, uninvolved hepatic parenchyma on left with well-differentiated hepatocellular carcinoma (HCC) on right, hematoxylin and eosin (H&E), ×100. B, Case 4, diffuse, strong LFABP staining in uninvolved hepatic parenchyma and HCC, ×100. C, Case 11, representative area of well to moderately differentiated HCC, H&E, ×100. D, Case 11, complete loss of LFABP staining, ×100. E, Case 16, moderately differentiated HCC on left, uninvolved hepatic parenchyma on right, H&E, ×100. F, Case 16, complete loss of LFABP staining in HCC with diffuse, strong LFABP staining in uninvolved hepatic parenchyma, ×100. G, Case 20, representative area of poorly differentiated HCC, H&E, ×100. H, Case 20, complete loss of LFABP staining, ×100. I, Case 17, Moderately to poorly differentiated HCC, H&E, ×40. J, Case 17, patchy, variably intense LFABP staining, ×40. A small portion of uninvolved hepatic parenchyma is seen at the right, with the most intense staining for LFABP.

Fig. 3

Moderately differentiated hepatocellular carcinoma (HCC), case 14. A, Uninvolved hepatic parenchyma on left with HCC on right, hematoxylin and eosin, ×100. B, Both the HCC and uninvolved hepatic parenchyma show diffuse, but weak, LFABP staining, ×100.