Novel Angiogenesis Markers as Long-Term Prognostic Factors in Patients With Renal Cell Cancer

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Abstract

To evaluate angiopoietin-2 (Ang-2) expression as a long-term prognostic factor in renal cell cancer (RCC) alone or in combination with MIB-1, Bcl-2, CD31 and VEGFR3 expressions a total of 224 RCC patients were included in this retrospective study. Ang-2 expression was significantly associated with tumor grade and stage as well as MIB-1, Bcl-2 and VEGFR3 expressions. Very high Ang-2 expression associated with better survival in RCC. These new markers should further be studied in prospective clinical trials.

Objective:

To evaluate Ang-2 expression alone and in combination with expression of cell proliferation and cell survival markers (MIB-1 and Bcl-2) and angiogenesis markers (VEGFR3 and CD31), and the associations of these markers with renal cell cancer (RCC) in long-term survival.

Patients and Methods:

Our study included 224 patients with RCC who were treated before the availability of antiangiogenic agents between 1985 and 1995, at the Pirkanmaa Hospital District in Finland. All tumor samples were reclassified and reevaluated by an experienced uropathologist, and parallel tissue microarrays (TMA) were performed for immunohistochemical analysis. Kaplan-Meier's survival estimation method and Cox proportional hazards models were used for survival analysis.

Results:

The percentage of Ang-2 expression in the tumor area varied from 0.07 to 25.65. Ang-2 expression was significantly associated with the tumor grade and stage, as well as the MIB-1, Bcl-2, and VEGFR3 expression (P = .042, P = .019, P = .039, P = .013, and P = .005, respectively). The highest Ang-2 expression predicted better survival, P < .05. High Bcl-2 and low MIB-1 expression combined with Ang-2 expression was associated with better survival. Multivariate analysis showed poorer survival in patients with low Ang-2 or high MIB-1 expressions: HR 1.89, 95% CI 1.16 to 3.08, P = .010 and HR 2.20, 95% CI 1.36 to 3.54, P = .001, respectively.

Conclusions:

Very high Ang-2 expression was associated with better survival in patients with RCC. Ang-2 expression correlated with tumor stage and grade, but it was still an independent prognostic factor in a multivariate analysis.

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