CXCR3-B Expression Correlates With Tumor Necrosis Extension in Renal Cell Carcinoma

Purpose: We investigated the expression of the 2 spliced variants of the CXCR3 receptor (CXCR3-A and CXCR3-B) and their ligands (MIG, IP-10 and I-TAC) in patients with renal cell carcinoma according to conventional prognostic factors and the necrosis pattern. Materials and Methods: A total of 59 patients with renal cell carcinoma were selected for study. Histotype, stage, grade and tumor diameter were first analyzed. Subsequently tumor necrosis extension, stratified as low-less than 30%, intermediate-30% to 75% and high-greater than 75%, was determined while blinded to pathological data, and CXCR3-B, IP-10, MIG and I-TAC mRNA levels were assessed. The overall correlation between CXCR3-B expression with the specific ligands, and tumor histotype, stage, grade, volume, necrosis extension and ligand expression were assessed on univariate and multivariate analyses. CXCR3-B levels stratified according to necrosis pattern were analyzed with the impaired t test. Results: CXCR3-B correlated with tumor necrosis and I-TAC (p = 0.0005 and 0.032, respectively). We did not note any correlation between CXCR3-B and histotype, stage, grade, diameter and expression of the other ligands IP-10 and MIG. Moreover, I-TAC did not correlate with tumor necrosis (p = 0.1102). In the multiple regression model a correlation between tumor necrosis and CXCR3-B expression was noted (p = 0.0005). Significant differences in CXCR3-B expression according to the necrosis pattern were observed between low and high, and between intermediate and high patterns (p = 0.0007 and 0.0183, respectively). Conclusions: Results demonstrate that CXCR3-B is an independent determinant factor for the extensive tumor necrosis pattern. These data emphasize the immunoangiostatic activity of the CXCR3/CXCR3 ligand biological axis for non-metastatic human renal cell carcinoma.