PROGNOSTIC VALUE OF MOLECULAR GENETIC MARKERS IN KIDNEY CANCER PATIENTS RECEIVING TARGETED THERAPY

Objective: to study the prognostic value of alterations in the VHL gene and the plasma markers hVEGF, hVEGFR2, and hVEGFR3 in patients with metastatic kidney cancer (KC) who receive targeted therapy.

Subjects and methods. Paraffin blocks from 22 patients with metastatic KC who received targeted therapy were analyzed for VHL gene mutation/methylation. Polymerase chain reaction (PCR) products were sequenced using a BigDye® Terminator v 3.1, a Cycle Sequencing Kit, and an ABI3100 genetic analyzer in accordance with the Applied Biosystems protocols. VHL gene methylation was determined by methyl-sensitive PCR. The markers hVEGF, hVEGFR2, and hVEGFR3 were measured in the plasma of 43 patients before, during, and after targeted therapy, by applying the commercial DuoSet® ELISA kits (RnDSystems, USA). The results obtained were analyzed by known statistical methods, by using the package of statistical programs SPSS 13.0 for Windows. Survival was estimated by the Kaplan-Meier method. Survival differences were found by the log-rank test in the patient groups. Cox uni- and multi-factorial regression analyses were used to identify factors that were prognostically significant for survival.

Results. Out of 22 patients, 10 (45.5 %) and 1 (4.5 %) were found to have VHL gene mutations or methylation, respectively. VHL gene inactivation did not affect prognosis in patients and the results of antiangiogenic therapy. Correlation analysis revealed no relationship between the concentrations of hVEGF and hVEGFR2 before and during therapy or absolute increases in hVEGF and hVEGFR2 concentrations during treatment with the frequency of progression during targeted therapy, with progression-free survival, and total life expectancy. No correlation was either found between the hVEGFR3 concentration and its changes and the results of antiangiogenic therapy. There was an inverse correlation between the pretreatment plasma hVEGFR3 level and lifetime without progression during antiangiogenic therapy (r = – 0.477, p = 0.039).

Conclusion. VHL gene alterations and plasma hVEGF and hVEGFR2 levels are not predictors of a response to antiangiogenic therapy. The pretreatment plasma hVEGFR3 level correlates with progression-free survival in KC patients receiving targeted therapy.

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