Related Experiment Video
Updated: Aug 19, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma
Mira Heinonen1, Petri Bono, Kirsi Narko
1Department of Pathology, University of Helsinki, Helsinki, Finland.
Insights
High cytoplasmic expression of Human Uridine Rich RNA Binding Protein (HuR) is linked to poorer breast cancer outcomes. This finding suggests HuR may serve as a prognostic marker for invasive ductal carcinoma.
Area of Science:
- Molecular Biology
- Oncology
- Pathology
Background:
- Human Uridine Rich RNA Binding Protein (HuR) is a key mRNA-binding protein involved in post-transcriptional gene regulation.
- HuR shuttles between the nucleus and cytoplasm, where it stabilizes specific mRNA transcripts.
- Nucleocytoplasmic translocation of HuR is essential for its function, prompting investigation into its role as a prognostic marker in cancer.
Purpose of the Study:
- To investigate the significance of HuR expression in breast cancer development and progression.
- To determine if cytoplasmic HuR expression serves as a prognostic indicator in invasive ductal breast carcinoma.
Main Methods:
- HuR expression was analyzed in a mouse mammary gland tumor model.
- Immunohistochemical analysis of HuR expression was performed on 133 human invasive ductal breast carcinoma specimens.
- Statistical analyses, including Cox multivariate modeling, were used to correlate HuR expression with clinicopathological features and patient survival.
Main Results:
- Elevated HuR expression, predominantly cytoplasmic, was observed in mouse mammary tumors.
- High cytoplasmic HuR immunoreactivity was detected in 29% of human breast cancer cases.
- Cytoplasmic HuR expression significantly correlated with high tumor grade, larger tumor size, and poorer 5-year distant disease-free survival (P < 0.0001).
Conclusions:
- High cytoplasmic HuR expression is associated with poor histologic differentiation and larger tumor size in ductal breast carcinoma.
- Cytoplasmic HuR is an independent prognostic factor for poor survival in breast cancer patients.
- HuR represents the first identified mRNA stability protein whose expression correlates with adverse outcomes in breast cancer.
Abstract:
HuR is a ubiquitously expressed mRNA-binding protein. Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer.
