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Abstract
The VEGFR-1 is suggested to promote tumor progression. In the current study we analyzed prevalence and prognostic impact of the VEGFR-1 by immunohistochemistry on a tissue microarray containing more than 3000 prostate cancer specimens. Results were compared to tumor phenotype, ETS-related gene (ERG) status, and biochemical recurrence. Membranous VEGFR-1 expression was detectable in 32.6% of 2669 interpretable cancers and considered strong in 1.7%, moderate in 6.7% and weak in 24.2% of cases. Strong VEGFR-1 expression was associated with TMPRSS2:ERG fusion status as determined by fluorescence in situ hybridization (FISH) and immunohistochemistry (p < 0.0001 each). Elevated VEGFR-1 expression was linked to high Gleason grade and advanced pT stage in TMPRSS2:ERG negative cancers (p = 0.0008 and p = 0.001), while these associations were absent in TMPRSS2:ERG positive cancers. VEGFR-1 expression was also linked to phosphatase and tensin homolog (PTEN) deletions. A comparison with prostate specific antigen (PSA) recurrence revealed that the 1.7% of prostate cancers with the highest VEGFR-1 levels had a strikingly unfavorable prognosis. This could be seen in all cancers, in the subsets of TMPRSS2:ERG positive or negative, PTEN deleted or undeleted carcinomas (p < 0.0001 each). High level VEGFR-1 expression is infrequent in prostate cancer, but identifies a subgroup of aggressive cancers, which may be candidates for anti-VEGFR-1 targeted therapy.
Highlights
Prostate cancer is the most prevalent cancer in men in Western societies [1]
Our findings demonstrate that high levels of VEGFR-1 protein expression are strongly linked to an adverse phenotype and early prostate specific antigen (PSA) recurrence of prostate cancer
VEGFR-1 immunostaining was localized in the membrane and the cytoplasm
Summary
Prostate cancer is the most prevalent cancer in men in Western societies [1]. the majority of prostate cancers behave in an indolent manner, a small subset is highly aggressive and requires extensive treatment [2,3]. Established pre-therapeutic prognostic parameters are limited to Gleason grade and tumor extent on biopsies, preoperative prostate specific antigen (PSA), and clinical stage. Studies on 113, 40, and 79 cancers had suggested a possible link between high VEGFR-1 expression levels and unfavorable tumor phenotype and poor disease outcome [21,22,25]. This observation was not confirmed by others analyzing cancers from 15 patients [23]. Our findings demonstrate that high levels of VEGFR-1 protein expression are strongly linked to an adverse phenotype and early PSA recurrence of prostate cancer
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