Prognostic role of HuR in hereditary breast cancer.
OBJECTIVE
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.


METHODS
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.
Department of Pathology/HUSLAB and Haartman Institute, Helsinki University Central Hospital, Finland.
Mira
M
Heinonen
Rainer
R
Fagerholm
Kirsimari
K
Aaltonen
Outi
O
Kilpivaara
Kristiina
K
Aittomäki
Carl
C
Blomqvist
Päivi
P
Heikkilä
Caj
C
Haglund
Heli
H
Nevanlinna
Ari
A
Ristimäki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016601:RNA-Binding Proteins