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Visualization of Protein-protein Interaction in Nuclear and Cytoplasmic Fractions by Co-immunoprecipitation and In Situ Proximity Ligation Assay
Published on: January 16, 2017
IGFBP-3 nuclear localization predicts human prostate cancer recurrence
David B Seligson1, Hong Yu, Sheila Tze
1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1738, USA.
Hormones & Cancer
|September 27, 2012
Summary
High nuclear expression of Insulin-like growth factor binding protein-3 (IGFBP-3) predicts prostate cancer recurrence. This finding may improve risk stratification for low-grade prostate cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Insulin-like growth factor binding protein-3 (IGFBP-3) is a tumor suppressor protein with known pro-apoptotic, anti-metastatic, and anti-angiogenic properties.
- Low serum IGFBP-3 levels are linked to increased risk of aggressive prostate cancer (PCa).
- The role of intracellular IGFBP-3 expression in PCa progression requires further investigation.
Purpose of the Study:
- To investigate the impact of nuclear and cytoplasmic IGFBP-3 protein expression in prostate cancer.
- To examine the in situ expression of IGFBP-3 across a spectrum of primary tumors using immunohistochemical analysis.
- To determine the association between IGFBP-3 expression and clinicopathological features, including tumor recurrence.
Main Methods:
- Immunohistochemical analysis of IGFBP-3 expression in prostate cancer tissue microarrays from 226 hormone-naïve patients.
- Semi-quantitative scoring of both cytoplasmic and nuclear IGFBP-3 expression based on intensity and positivity.
- Statistical analysis to correlate IGFBP-3 expression with clinicopathological variables and tumor recurrence.
Main Results:
- Tumor tissues exhibited higher cytoplasmic and nuclear IGFBP-3 staining compared to benign tissues.
- Significantly higher nuclear IGFBP-3 staining was observed in PCa compared to benign prostatic hyperplasia, normal prostate, and prostate intraepithelial neoplasia.
- Higher nuclear IGFBP-3 expression, both continuous and dichotomized, was significantly associated with PCa recurrence.
- Cytoplasmic IGFBP-3 staining showed no significant association with recurrence in any subgroup.
- In low-grade PCa, nuclear IGFBP-3 positivity was a stronger predictor of recurrence than PSA, margin status, TNM stage, or capsular invasion.
Conclusions:
- Nuclear IGFBP-3 expression is significantly elevated in prostate cancer and is strongly associated with tumor recurrence.
- Cytoplasmic IGFBP-3 expression does not appear to be a significant predictor of recurrence.
- High nuclear IGFBP-3 expression is a potent predictor of recurrence in low-grade prostate cancers, suggesting its utility in risk stratification.
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