Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) Is Up-Regulated in Prostatic Adenocarcinoma (PAC) and Correlates with Gleason Grade
KD Linos, S Lu, JS Ross, TA Jennings, BM Mian, HAT Nazeer, CE Sheehan, T Nazeer. Albany Medical College, Albany, NY
Background: Insulin-like growth factor (IGFs) signaling pathway components and its docking molecules are associated with regulation of cell growth, differentiation, establishment of neoplastic phenotype and apoptosis. Carrier proteins such as IGF binding protein 3 (IGFBP-3) are modulators of IGF actions and are known to demonstrate proapoptotic and inhibitory effects. Abnormalities of the IGF axis have been reported in breast and lung cancers. However, published data are contradictory regarding its association with PAC with some studies showing a positive correlation. To clarify this we studied its expression in PAC.
Design: Formalin-fixed paraffin-embedded whole-mount radical prostatectomy tissue sections from a representative block from 199 patients with PAC were evaluated for IGFBP3 expression by immunohistochemistry. Hematoxylin and Eosin stained slides were reviewed and tumors graded based on the Gleason grading system in all cases. Sections were stained by automated methods (Ventana Medical Systems, Tucson, AZ) using mouse anti-human IGFBP-3 antibody (MAB305; R&D Systems, Minneapolis, MN). Tumors were scored semi-quantitatively based on staining intensity (weak, moderate, strong) and distribution (focal, regional, diffuse). These results were tested for correlations with Gleason grade and tumor stage.
Results: IGFBP-3 immunoreactivity was cytoplasmic in the positive cases. Cytoplasmic IGFBP-3 over expression was observed in 119/199 (60%) of all tumors. 144/199 (72%) patients received no therapy prior to radical prostatectomy. Within the non-treated subgroup, cytoplasmic over expression correlated with high tumor Gleason grade (Gleason score of 7 or more) [65% high grade versus 48% low grade, p=0.042]. There was a trend towards advanced stage, with 66% advanced stage tumors over expressing IGFBP3 protein versus 51% organ confined tumors, p=0.10).
Conclusions: IGF-BP3 is up-regulated in PAC and correlates with high tumor grade suggesting its role in prostate cancer pathogenesis. Further studies are warranted to investigate prostate cancer management through manipulation of the IGF axis.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 127, Monday Morning