HuR expression in the nucleus correlates with high histological grade and poor disease-free survival in ovarian cancer

Background: HuR, a nucleo-cytoplasmic shuttling protein, plays an important role in mRNA stability as well as cellular differentiation. Recently, HuR expression, particularly in the cytoplasm, was thought to be associated with the prognosis of several cancers including ovarian cancer. Aims: To study the clinical significance of nuclear HuR expression in ovarian cancer. Methods: Primary epithelial ovarian carcinomas (102) and ovarian low malignant potential tumours (11) were assessed for HuR protein expression by immunohistochemistry. HuR scoring accounted for both intensity and percentage of cells stained, and ranged from 0 to 300. Results: HuR was found to be present predominantly in the nucleus, where it was expressed in 85.8% of cases. Nuclear HuR was associated with the invasive cancers (P = 0.004), high grade (P < 0.0001), large residual disease (P = 0.045) and poor disease-free survival (P = 0.0009). Among those 91 specimens with high grade, 76.9% had a high nuclear HuR score, while in those 22 cases with low grade, only 31.8% had a high HuR score (P < 0.0001). Multivariate analysis showed that nuclear HuR intensity was an independent prognostic factor for poor disease-free survival (P = 0.0484). When the invasive cancers were analysed separately, only the association between nuclear HuR and high grade remained (P = 0.0089). Conclusions: Our results support the clinical significance of nuclear HuR in ovarian carcinoma and suggest that nuclear HuR may also play a role in the biology of ovarian cancer. These data suggest a more complex model for HuR in ovarian cancer than one limited to cytoplasmic localisation.