Semaphorin 4F as a Critical Regulator of Neuro-Epithelial Interactions and a Biomarker of Aggressive Prostate Cancer
Dandan He, Yi Ding, Diego Florentin, Michael Ittmann, Gustavo Ayala. University of Texas Health Sciences Center Medical School, Houston, TX; Baylor College of Medicine, Houston, TX
Background: Cancer related axono-neurogenesis is a recently described biologic phenomenon. Semaphorin 4F (S4F) is a member of family of proteins with roles in embryological axon guidance and is also expressed in adults. S4F produced by prostate cancer cells is a key regulator of the interactions between nerves and cancer cells.
Design: Tissue microarrays from radical prostatectomy specimens with PCa (350 patient) were immunostained with against S4F antibodies developed by us. Slides were imaged using image deconvolution imaging and analyzed using image segmentation technology. Data is provided on a cell per cell basis (nuclear vs. cytoplasmic), per tumor compartment, per patient. Data was correlated with pertinent clinico-pathological parameters, other biomarkers and survival analysis performed. To unders tand the heterogeneity of S4F expression we used an unsupervised clustering algorithm.
Results: S4F expression was found in the cytoplasm/nuclei of epithelial PCa and reactive stroma and was over expressed in HGPIN and PCa. Nuclear/cytoplasmic PCa and stromal S4F expression had differential expression patterns of heterogeneity. Patients with high values of S4F in PCa cytoplasm are at significantly higher risk of biochemical recurrence, by univariate and multivariate analysis (p=0.0007, HR=7.551). S4F cytoplasmic expression in PCa cells also correlates with nerve density in PCa and perineural invasion diameter, corroborating involvement of this molecule in PCa induced axonogenesis and perineural invasion. Significant correlations were identified with NFkB and inversely with apoptosis in PNI. The cell-per-cell expression unsupervised clustering resulted in grouping of the patients with biochemical recurrence (fig 1), confirming that this novel way of measuring and analyzing biomarker has the potential to produce unique data.
Conclusions: This data demonstrates that S4F is involved in human PCa progression and regulates the interaction between cancer and nerves. This also demonstrates our ability to study biomarker in tumor compartments with state of the art quantitative methods.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 72, Tuesday Morning