Evaluation of CD24 Expression in Matched Primary and Metastatic Muscle Invasive Urothelial Carcinoma Tissues
SC Smith, G Kristiansen, DE Hansel, D Theodorescu. UVA Health System, Charlottesville, VA; University Hospital Zurich, Zurich, Switzerland; Cleveland Clinic Foundation, Cleveland, OH
Background: A growing body of literature has implicated the GPI-linked glycoprotein, CD24, as both a prognostic biomarker and mediator of metastasis, potentially through regulation of integrin-mediated cell adhesion and signaling. We have recently observed that in vivo selection of lung metastatic clones from parental muscle invasive urothelial carcinoma (MIUC) cells through nude mice results in selection of highly CD24 expressing cells. In this study, we wished to examine whether the expression of CD24 in matched human primary MIUC tumors and nodal metastases was consistent with a selective advantage for CD24 expressing cells in metastasis.
Design: A tissue microarray was constructed of node positive high grade MIUC cystectomy specimens using triplicate 1.5-mm cores from paired primary and node tissue blocks (N=70 pairs). Automated IHC staining of the array used the mAb SWA-11 with DAB as chromogen. Staining was scored by intensity (0-3; negative, low, moderate, or intense) and by proportion (0-2; 0%, <50%, >50%). Intensity and proportion staining data for matched primary and nodal metastases were compared by correlation, paired Wilcoxon two-sample tests, and chi-square tests.
Results: Overall we observed a significant correlation between primary and metastases as regards intensity and proportions of staining (rs=0.49 and 0.56, respectively, both P<0.01). However, paired metastases exhibited significantly higher CD24 staining intensity and proportion compared to their paired primaries (both P<0.01), as in this striking example:
Neither age, sex, T stage, ±LVSI, or ± margins were associated with CD24 level.
Conclusions: We observed a significant increase in intensity and proportion of CD24 staining in paired nodal metastases compared to primary MIUCs. This observation is consistent with either selection of CD24 positive cells in vivo, as we have observed in model systems, or with a novel mechanism resulting in induction of its expression in situ in the node. Ongoing studies are delineating the mechanism of this phenomenon.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 147, Wednesday Afternoon