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Prognostic Role of HuR in Hereditary Breast Cancer

Author's Affiliations: Departments of ¹ Pathology/HUSLAB and Haartman Institute, ² Obstetrics and Gynecology, ³ Oncology, ⁴ Clinical Genetics, and ⁵ Surgery, Helsinki University Central Hospital; and ⁶ Genome-Scale Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

Requests for reprints: Ari Ristimäki, Genome-Scale Biology Program, Biomedicum Helsinki, Room B529b, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 Helsinki, Finland. Phone: 358-9-191-25588; Fax: 358-9-191-26700; E-mail: Ari.Ristimaki{at}helsinki.fi.

Purpose: HuR is an mRNA-binding protein that enhances the stability of certain transcripts and can regulate their translation. Elevated cytoplasmic expression of HuR protein has been linked to carcinogenesis and is associated with reduced survival in breast, ovarian, and gastric adenocarcinomas.

Experimental Design: Here, we have explored the relevance of HuR in familial breast cancer. Tumor samples were collected from patients with identified BRCA1 (n = 51) or BRCA2 (n = 47) mutations or familial non-BRCA1/2 cases (n = 525), and analyzed by immunohistochemistry.

Results: Among familial non-BRCA1/2 breast cancer patients, cytoplasmic HuR protein expression was present in 39.4% of the cases and was associated with estrogen receptor negativity, progesterone receptor negativity, p53 positivity, high tumor grade, and ductal type of the tumor. In multivariate analysis, cytoplasmic HuR expression was an independent marker of reduced survival in the non-BRCA1/2 group along with tumor size >2 cm, lymph node metastasis, and high histologic grade. In patients with BRCA1 or BRCA2 mutations, cytoplasmic HuR expression was more frequent (62.7% for BRCA1 and 61.7% for BRCA2) than in the non-BRCA1/2 group, but in BRCA-mutated subgroups cytoplasmic HuR expression did not associate with survival.

Conclusions: Our results show that HuR is an important prognostic factor in familial breast cancer patients and may contribute to carcinogenesis in this disease.

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