Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma - PubMed (original) (raw)

Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma

D Yoshikawa et al. Br J Cancer. 2008.

Abstract

Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered as potential therapeutic targets in cholangiocarcinoma, but no studies have yet clarified the clinicopathological or prognostic significance of these molecules. Immunohistochemical expression of these molecules was assessed retrospectively in 236 cases of cholangiocarcinoma, as well as associations between the expression of these molecules and clinicopathological factors or clinical outcome. The proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4, 53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and 8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively. Clinicopathologically, EGFR overexpression was associated with macroscopic type (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate analysis showed that EGFR expression was a significant prognostic factor (hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.52-4.69; P=0.0006) and also a risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05-3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma.

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Figures

Figure 1

Figure 1

Representative immunohistochemical staining of (A) EGFR, (B) HER2, and (C) VEGF in cholangiocarcinoma (× 400 magnification). (D) Epidermal growth factor receptor tends to be expressed in the poorly differentiated component (× 100 magnification). (E) Human epidermal growth factor receptor 2 is preferentially expressed in more differentiated areas such as the glandular or papillary component (× 100 magnification).

Figure 2

Figure 2

Survival curves stratified by EGFR expression in (A) IHCC and (B) EHCC (Kaplan–Meier method). The outcome of EGFR-positive cases was significantly worse than that of EGFR-negative cases in both IHCC (_P_=0.0008) and EHCC (_P_=0.0204) (by log-rank test).

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