Biologic significance of fascin expression in clear cell renal cell carcinoma: Systematic analysis of primary and metastatic tumor tissues using a tissue microarray technique

ObjectivesTo 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).MethodsA 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.ResultsFascin 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.ConclusionsFascin 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.