Author information
1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: hechtmaj@mskcc.org.
2
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
3
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Weill Cornell Medical College, New York, NY 10065, USA.
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: shiaj@mskcc.org.
Abstract
Mutations of Hepatocyte-Nuclear-Factor-1-Homeobox-A gene and loss of Liver-Fatty-Acid-Binding-Protein are well documented in hepatocellular adenoma. However, the role of Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations in hepatocellular carcinoma remains to be determined. In this study, all hepatocellular neoplasms evaluated by our institutional Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Clinical Targets assay or the Cancer Genome Atlas sequencing, and cases reported in the literature, were queried for Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations. Together, 11 of 672 (1.6%) hepatocellular carcinomas harbored Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations. The single case from our institution (n=153) was extremely well differentiated, arising in a background of adenomatosis. Both the adenoma and carcinoma component contained the same 2 somatic Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations (p. E32* and L214Q), with loss of Liver-Fatty-Acid-Binding-Protein. From the literature, 2 of 146 (1.4%) hepatocellular carcinomas had Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations, and both arose in a background of adenomatosis. Information on pre-existing adenoma for the remaining cases (8/373, from The Cancer Genome Atlas) was not available. Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations in carcinomas were associated with negative viral hepatitis status (P=.004), mutually exclusive with Catenin-Beta-1 hotspot mutations, and trended to occur more in females (P=.06) and without cirrhosis (P=.03). Grade was not associated with Hepatocyte-Nuclear-Factor-1-Homeobox-A status (P=.28). Somatic Hepatocyte-Nuclear-Factor-1-Homeobox-A mutations occur in approximately 1-2% of hepatocellular carcinoma, often in a background of adenomatosis. Our findings suggest that malignant transformation of Hepatocyte-Nuclear-Factor-1-Homeobox-A mutated hepatocellular adenoma occurs, albeit infrequently. Hepatocellular adenomas with Hepatocyte-Nuclear-Factor-1-Homeobox-A mutation or adenomatosis with loss of Liver-Fatty-Acid-Binding-Protein warrant thorough sampling and examination.