Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Gallbladder cancer (GBC) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (ERα, ERβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (NT), and determined their prognostic impact. Immunohistochemical (IHC) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERβ, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%, 100% of NT, respectively. No ERα expression was found in GBC and NT. Strong (3+) HER2 expression by IHC or HER2 amplification was seen in five GBC (10.4%). A positive correlation was found between HER2 and CTGF and ERβ expression in GBC and matched NT. In the multivariate analysis, patient age >70 years, tumor size and ERβ expression in GBC was highly predictive for OS (p = 0.003). The correlation between HER2, CTGF and ERβ expression in GBC and NT may indicate the interaction of these pathways in physiological processes and gallbladder pathology.