CXCR3-B expression correlates with tumor necrosis extension in renal cell carcinoma.
OBJECTIVE
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.


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 unpaired 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 nonmetastatic human renal cell carcinoma.
Gacci
Mauro
M
Department of Urology, University of Florence, Florence, Italy. maurogacci@yahoo.it
Serni
Sergio
S
Lapini
Alberto
A
Vittori
Gianni
G
Alessandrini
Marco
M
Nesi
Gabriella
G
Palli
Domenico
D
Carini
Marco
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D046509:Tissue Culture Techniques
D014408:Biomarkers, Tumor; D054371:Chemokine CXCL11; C104577:IP10-Mig receptor; D054367:Receptors, CXCR3; D018121:Receptors, Cytokine