The Prognostic Value of the Metastasis Suppressor, RhoGDI2, in Muscle Invasive Urothelial Carcinoma
SC Smith, DE Hansel, HF Frierson, D Theodorescu. UVA Health System, Charlottesville, VA; Cleveland Clinic Foundation, Cleveland, OH
Background: RhoGDI2 expression suppresses metastasis in muscle invasive urothelial carcinoma (MIUC) cell line experimental metastasis models, and in one small study of nodal negative MIUC tissues, reduced RhoGDI2 expression has been shown to be independently associated with decreased survival. Given the importance of validating candidate biomarkers in independent cohorts, in this study we investigated RhoGDI2 staining in a larger new cohort of MIUC tissues, including matched primary and nodal metastases.
Design: A tissue microarray composed of 122 MIUCs and 70 additional matched nodal metastases was used for immunohistochemical staining with a polyclonal antibody specific for RhoGDI2. Staining was scored as negative, low positive, or positive. Association of RhoGDI2 expression with clinicopathologic parameters was undertaken by chi-square tests, Kaplan-Meier curves, and Cox proportional hazards regression analyses. Matched primary and nodal metastases were compared by correlation and Wilcoxon paired two sample tests.
Results: RhoGDI2 staining was not associated with stage, grade, age, gender, or LVSI, while in a univariate or multivariate fashion RhoGDI2-negative staining was associated with decreased disease specific survival (P=0.03 and 0.05).
RhoGDI2-negative staining was significantly associated with nodal metastasis (P=0.02), significantly correlated between matched primary and nodal tissues (r=.54, P<0.01), and frequently reduced in the nodal metastases compared to primary tissues (P<0.01). A nonsignificant trend toward association between negative RhoGDI2 staining and development of distant metastasis during follow-up was noted (P=0.08).
Conclusions: We confirmed prior findings of association of reduced RhoGDI2 with decreased disease specific survival, while observing new associations with nodal or distant metastasis, supporting its role in suppression of these processes. The significant correlation of RhoGDI2 expression in primary and nodal tissues supports prior observations suggesting that loss of metastasis suppressor expression should predominate in the primary tumor. Validation of this promising biomarker in additional cohorts is ongoing.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 146, Wednesday Afternoon