Hepatocelluar carcinoma associated with attenuated familial adenomatous polyposis: a case report and review of the literature

Abstract

Hepatocelluar carcinoma (HCC) has rarely been associated with familial adenomatosis polyposis (FAP). Between 1950 and 2011, only a few cases of HCC associated with classic FAP have been reported in the medical literature. Here, we report the first case to our knowledge of HCC associated with attenuated FAP (aFAP). The patient possessed a single nucleotide mutation in the noncoding region after exon 4, which is rarely observed in attenuated FAP, and not previously reported in classic FAP–associated HCC. Our patient underwent liver transplantation for a 22-cm-large HCC (in China), however, her HCC recurred 1.5 years after the transplantation. Here we review the medical literature on FAP and HCC, with a particular focus on the role of the Wnt/APC/β-catenin pathway toward a better understanding of HCC pathogenesis.

Figure 1

(A) Magnetic Resonance Image (MRI) of the Liver, Showing a Large Primary Hepatocellular Carcinoma About 22.5 cm in Size. (B) Microscopic View of a Core Biopsy, Revealing Hepatocellular Carcinoma With Mature Hepatocytes Arranged in Rosettes and Thickened Groups, and With Mild Cytologic Atypia. Hematoxylin and Eosin Stain at ×100 Magnification. (C) MRI of the Liver Showing 3 Recurrent Lesions in the Transplanted Liver. (D) Microscopic View of a Core Biopsy, Again Confirming Hepatocellular Carcinoma at ×100 Magnification

Figure 2

The Potential Role of Wnt/APC/β-Catenin Pathway in APC Gene-Mutated Hepatocarcinogenesis. The Wnt-Ligand is a Secreted Glycoprotein That Binds to Frizzled Receptors (Fz), Which Trigger a Cascade and Result in the Release of the Multifunctional Kinase GSK-3β Form the APC/Axin/GSK-3β Complex. In Normal Hepatocytes, in the Absence of Wnt-Signal (Off State), β-Catenin, is Targeted for Degradation by the APC/Axin/GSK-3β Complex. β-Catenin Undergoes Proteasomal Degradation After Phosphorylation by CK1α and GSK-3β. In Tumor Cells, Mutated or Truncated APC Protein Cannot Form the APC/Axin/GSK-3β Complex, Resulting in Stabilization of the β-Catenin Level. β-Catenin Translocates into the Nucleus and is Recruited to the LEF/TCF DNA-Binding Factors and Subsequently Leads to the Activation of Wnt-Targeted Genes