Expression of transcription factor AP-2alpha predicts survival in epithelial ovarian cancer

Abstract

The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2alpha was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2alpha antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2alpha was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2alpha protein only in the cytoplasm. In carcinomas nuclear AP-2alpha expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2alpha varied according to the histological subtype and differentiation. AP-2alpha and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13-2.18, P= 0.007) the high cytoplasmic AP-2alpha expression favoured the overall survival. In contrast, the nuclear AP-2alpha expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13-3.83, P= 0.018). The shift in the expression pattern of AP-2alpha (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2alpha in ovarian cancer may be due to post-transcriptional regulation.