CD47 is not Over-Expressed in Fibrolamellar Hepatocellular Carcinoma.

OBJECTIVES: CD47 is a transmembrane receptor that inhibits phagocytosis. Over-expression of CD47 is associated with an increased risk of tumor growth and metastasis. Clinical trials based on anti-CD47 therapy in adults are underway in a variety of malignancies. CD47 has been shown to be over-expressed in conventional hepatocellular carcinoma (HCC), a common liver tumor in adults. To our knowledge, there have been no studies to evaluate CD47 expression in the fibrolamellar subtype of HCC (FL-HCC), common in children and young adults. This study will evaluate CD47 expression in FL-HCC and shed light on its suitability for anti-CD47 therapy.

METHODS: Using immunohistochemistry, 10 samples of FL-HCC from 8 patients were evaluated for CD47 (anti-phagocytic) and calreticulin (pro-phagocytic) expression. By direct comparison, CD47 and calreticulin expression were evaluated in 21 samples of conventional HCC. Additionally, transcriptome sequencing to detect CD47 mRNA expression was performed on fresh tissue from 1 FL-HCC institutional patient and previously published sequencing data from 20 additional samples was reviewed.

RESULTS: Immunohistochemistry showed only weak CD47 expression in 20% of FL-HCC samples. In contrast, 57% of conventional HCC samples showed CD47 expression. All (100%) FL-HCC samples showed moderate or strong calreticulin expression. The difference between CD47 and calreticulin expression in FL-HCC is statistically significant ( p =0.0007). Transcriptome sequencing revealed no difference in CD47 expression between FL-HCC and normal liver samples.

CONCLUSIONS: CD47 is not over-expressed in FL-HCC. Our studies provide no support for expanding ongoing clinical trials in adults to include children and young adults with FL-HCC.