Insulin-like growth factor binding protein-3 (IGFBP-3) is a pro-apoptotic, anti-metastasic, and anti-
angiogenic protein. Low serum
IGFBP-3 has been associated with risk of more aggressive
prostate cancer (PCa). We investigated the impact of nuclear and cytoplasmic
IGFBP-3 protein expression levels in PCa by examining their in situ expression across a wide spectrum of primary
tumors by immunohistochemical analysis of tissue microarrays. Immunohistochemistry was performed on PCa microarrays constructed from 226
hormone naïve patients who underwent radical
prostatectomy. Both cytoplasmic and nuclear
IGFBP-3 expressions were scored in a semi-quantitative fashion using an integrated measure of intensity and positivity. The distribution of
IGFBP-3 protein expression was examined across the spectrum of epithelial tissues, and its association with standard clinicopathological covariates and
tumor recurrence was examined. There was a broad range of
IGFBP-3 staining across all histologies examined.
Tumor had higher
IGFBP-3 cytoplasmic and nuclear staining than benign histologies. For
IGFBP-3 nuclear staining, PCa was significantly different than
benign prostatic hyperplasia, normal prostate, and prostate intraepithelial
neoplasia. As both a continuous and dichotomized variable, higher nuclear
IGFBP-3 expression had statistically significant associations with PCa recurrence. The cytoplasmic staining had no significance in any patient subgroup. In patients with low-grade
cancer,
IGFBP-3 nuclear positivity was a better predictor of recurrence than baseline PSA,
tumor margin status, TNM
tumor stage, or presence of capsular invasion. High nuclear
IGFBP-3 is amongst the strongest predictors of
cancer recurrence in patients with low-grade
prostate cancers and may therefore play an important role in risk stratification.