The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma

Purpose: Through its binding with interferon inducible angiostatic chemokines the chemokine receptor CXCR3 has an important role in regulating tumor mediating immunity, angiogenesis and metastatic spread. To evaluate its role in the biology of clear cell renal cell carcinoma we performed a tissue microarray based study. Materials and Methods: The tissue microarray comprised 154 patients who underwent nephrectomy for localized (N0M0) clear cell renal cell carcinoma at UCLA from 1989 to 2000. Immunohistochemical staining was evaluated by 2 anatomical pathologists who were blinded to outcome. The end point of this study was disease-free survival. Median followup was 5.9 years. Results: A total of 96% of the tumor specimens stained positive for CXCR3. The mean percent of cells staining positive was 68% (range 0 to 100%). CXCR3 expression was not associated with other common clinicopathological features, such as Eastern Cooperative Oncology Group performance status, T stage, Fuhrman grade, vascular invasion or sarcomatoid features. Patients with low CXCR3 expression (less than 30%) had a significantly worse prognosis than patients with high CXCR3 expression with a 5-year disease-free survival rate of 57% vs 82% (p = 0.009). Multivariate Cox regression analysis retained T stage, Eastern Cooperative Oncology Group performance status, sarcomatoid features and CXCR3 as independent prognostic factors. Conclusions: CXCR3 is a novel molecular marker in patients with clear cell renal cell carcinoma. Its higher expression is an independent predictor of improved disease-free survival following nephrectomy for localized disease. Since CXCR3 is not associated with other clinicopathological prognostic factors, it may represent an ideal complementary molecular marker for identifying patients who are at higher risk for recurrence after nephrectomy.