A Case of Intrahepatic Cholangiocarcinoma With Epidermal Growth Factor Receptor Expression: Possible Marker for Targeted Chemotherapy

Abstract

Cholangiocarcinoma is an aggressive malignancy that presents with widespread metastasis at the time of diagnosis and a low resectability rate. Epidermal growth factor receptor (EGFR) expression offers a possible avenue for targeted chemotherapy (Jimeno et al, 2005 and Wiedmann et al, 2006). A 58-year-old woman presented with abdominal pain, fatigue and recent weight loss. At imaging, the right hepatic lobe contained an 8.5 x 7 cm mass with multiple satellite hepatic lesions, but no lesions elsewhere. Serum CA-125 level was elevated at 501 U/mL, while CA19-9, alpha-fetoprotein and carcinoembryonic antigen levels were within normal limits. At biopsy, the lesion consisted of mucin secreting (mucicarmine positive) malignant glands with significant tumor necrosis in a sclerotic background. Tumor cells were also immunoreactive for cytokeratin-7, cytokeratin-20, epithelial membrane antigen, polyclonal/monoclonal carcinoembryonic antigen, EGFR (strong, 3+) and CA-125. Estrogen receptor was only weakly positive. Hepar-1, CDX-2, Thyroid transcription factor-1, CA19-9, gross cystic disease fluid protein-15, progesterone receptor and Her2/Neu immunomarkers were all negative. This profile excluded common extrahepatic primaries and a diagnosis of mucin producing intrahepatic cholangiocarcinoma was made. Bile acid-activated EGFR may promote progression of cholangiocarcinoma, with a 5-year survival of 20% in EGFR positive cases as compared to 60% in EGFR negative cases (Shafizadeh et al, 2010). Yoshikawa et al (2008) also documented that EGFR expression correlated with lymph node metastasis, tumor progression, advanced tumor stage, and a decreased 5 year survival. We recommend that EGFR testing should be a routine part of immunohistochemical profiling of adenocarcinoma in the liver as EGFR expression could predict a poorer outcome, but also potentially offer a marker for anti-EGFR chemotherapy with improved survival.