Biologic Significance of Fascin Expression in Clear Cell Renal Cell Carcinoma: Systematic Analysis of Primary and Metastatic Tumor Tissues Using a Tissue Microarray Technique

Objectives: To investigate the biologic significance of fascin, a globular actin cross-linking protein, involved in cell adhesion and motility, in primary and metastatic renal cell carcinoma (RCC).

Methods: A total of 136 primary clear cell RCCs and 54 clear cell RCC metastases were stained immunohistochemically using a tissue microarray technique. Distinct cytoplasmic staining was considered positive, and the staining results were associated with the pT stage, Fuhrman grade, tumor size, sarcomatoid morphology, and metastasis-free survival. For multivariate testing, Cox's proportional hazards regression model was used.

Results: Fascin expression was noted in 13 (10%) of 136 primary and 25 (46%) of 54 metastatic RCC specimens (P <0.001). Fascin expression was associated with high tumor stage (2 [3%] of 70 pT1 versus 11 [17%] of pT2/pT3; P = 0.008), high tumor grade (3 [3%] of 88 grade 1-2 versus 10 [21%] of 48 grade 3-4; P = 0.002), and large tumor size (P <0.001). In addition, 8 (62%) of 13 RCCs with sarcomatoid morphology expressed fascin compared with 5 (4%) of 123 RCCs without sarcomatoid transformation (P <0.001). Metastatic disease was noted in 10 (77%) of 13 patients with fascin-positive RCC compared with 26 (21%) of 121 patients with fascin-negative RCC (P <0.001). Multivariate analysis revealed pT Stage 1 or greater (P <0.001, risk ratio [RR] 8.6, 95% confidence interval [CI] 2.8 to 26.5), Fuhrman grade greater than 2 (P <0.001, RR 12.7, 95% CI 4.6 to 35.4), fascin expression (P <0.001, RR 7.2, 95% CI 3.0 to 17.4), and female gender (P = 0.02, RR 2.5, 95% CI 1.1 to 5.5) as independent predictors of metastatic disease.

Conclusions: Fascin immunoreactivity in RCC proved to be an independent predictor of metastatic disease and was demonstrated in almost one half of RCC metastases. Thus, fascin may be a promising molecular target for future cancer therapy.