Epithelial Growth Factor Receptor Mutations Predict Hepatocellular Carcinoma Patient’s Prognosis

Abstract

Objective: Hepatocellular Carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer-related death in the world. Epithelial Growth Factor Receptor (EGFR) overexpression has been demonstrated in HCC patients frequently and is a poor prognostic factor. EGFR is a promising target for cancer treatment, but its variety in response by mutation status. Patients and Methods: We retrospective analyzed 28 Hepatocellular Carcinoma (HCC) patients with good quality DNA samples, 5 hepatic dysplasia tissues, and 5 cholangiocarcinoma samples from 1996 to 2002. EGFR mutation status was detected by ARMS and Scorpions real-time PCR, using therascreen® EGFR RGQ PCR Kit. T790M, exon 19 deletions, L858R, L861Q, G719X, S786I, and exon 20 insertions can be detected. Clinical data of 28 HCC patients were collected for the longest period of 17 years. Results: All patients received liver segmentectomy. No one received tyrosine kinase inhibitor treatment during the following period. All liver samples had T790M mutation detected. Based on overall survival, we calculated cut-off points, by ROC curve. In HCC patients with a higher percentage of T790M or G719X mutations had better overall survival (P=0.001, and 0.036). Patients with exon 19 deletion showed a trend of better overall survival. HCC patients with exon 19 deletions, L858R and G719X mutations showed trends of longer Disease Free Survival (DFS) and HCC patients with higher S768I mutation had a trend of shorter DFS. HCC samples from chronic hepatitis B carriers had a higher T790M mutation rate and the ones from chronic hepatitis C carriers showed the opposite in T790M mutation with statistics significant (P=0.013). No EGFR mutations contribute to HCC recurrence. Conclusion: EGFR mutation status can predict HCC patient’s prognosis post liver segmentectomy.