Introduction

Neuropilin 2 (NRP2) as co-receptor for the VEGF-C-receptor has to been shown highly expressed and seems to be associated with worse outcome for survival in several tumour entities._x000D_ Here, we investigated the expression of NRP2 in prostate cancer and correlated it with the overall survival (OS) and cancer-specific survival (CSS) in patients with prostate cancer (PCa)._x000D_

Methods

For the generation of a tissue microarray (TMA), prostate tissue specimens were used from 400 patients with localized PCa undergoing radical prostatectomy (RP) between 1996 and 2005. Follow-up data regarding OS and CSS were obtained. Patients were stratified according to prognostic high-risk factors in PCa: pT≥3, GS≥8, pN1. Diagnostic hematoxylin and eosin stained tissue sections from the RP specimen were reviewed and representative tumor areas were assigned. From these areas each six tumor cores and two tumor-free cores were selected per patient and mounted into a total of 14 paraffin blocks. The protein expression of VEGF-C and NRP2 was analyzed by immunohistochemistry. The intensity of membranous staining of VEGF-C and NRP2 was assessed in four categories (0-3). For statistics, the mean of the intensity values in all PCa tissues cores per patient was calculated and correlated with clinicopathological and survival parameters. The prognostic impact of expression of VEGF-C (≤ median vs. > median) and of NRP2 (signal vs. no signal) was assessed by Kaplan-Meier analyses for CSS and OS and by log-rank test. Uni- and multivariate Cox&[prime]s proportional hazard regression analyses were performed to assess the independent prognostic impact of NRP2 and VEGF-C.

Results

The median follow-up was 10a (0.34-17.6a). In patients with evidence of NRP2 expression, the mean CSS was 15.5a whereas in patients without expression of NRP2 the mean CSS was 16.1a (p=0.007). Especially patients with high-risk PCa and without evidence of NRP2 expression showed a significantly longer CSS than patients with NRP2 expression (pT2 vs. pT≥3: 15.5a vs. 12.3a; p=0.05; GS≤7 vs. GS≥8: 15.6a vs. 14.4a; p=0.024; pN0 vs. pN1: 15.4a vs. 13.3, p=0.018). In multivariate analysis, the NRP2 expression emerged as an independent predictor for the CSS in all patients (HR 2.36; 95%-CI 1.17-4.71; p=0.016) as well as in the subgroups. However, there was no significant association between the NRP2 expression and the OS. Furthermore, the VEGF-C expression was associated neither with OS nor with CSS.

Conclusions

The expression of NRP2 in PCa is significantly associated with a shorter CSS and might be an independent prognostic factor for the CSS especially in patients with high-risk PCa.

Funding

none