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Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer.
- Source :
-
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2009 Dec; Vol. 22 (12), pp. 1564-74. Date of Electronic Publication: 2009 Sep 04. - Publication Year :
- 2009
-
Abstract
- Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n=1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (P<0.001), small tumors (P<0.001), estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P=0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibody Specificity
Biomarkers, Tumor analysis
Biomarkers, Tumor immunology
Breast Neoplasms mortality
Cell Line, Tumor
Cohort Studies
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Ki-67 Antigen analysis
Middle Aged
Proportional Hazards Models
Proto-Oncogene Mas
RNA Interference
RNA-Binding Proteins immunology
Randomized Controlled Trials as Topic
Receptors, Estrogen analysis
Risk Assessment
Time Factors
Tissue Array Analysis
Treatment Outcome
Up-Regulation
Antineoplastic Agents, Hormonal therapeutic use
Biomarkers, Tumor metabolism
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Cell Nucleus metabolism
RNA-Binding Proteins metabolism
Tamoxifen therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0285
- Volume :
- 22
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Type :
- Academic Journal
- Accession number :
- 19734850
- Full Text :
- https://doi.org/10.1038/modpathol.2009.124