VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy
AbstractThe 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. View Full-Text
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Tsourlakis, M.C.; Khosrawi, P.; Weigand, P.; Kluth, M.; Hube-Magg, C.; Minner, S.; Koop, C.; Graefen, M.; Heinzer, H.; Wittmer, C.; Sauter, G.; Krech, T.; Wilczak, W.; Huland, H.; Simon, R.; Schlomm, T.; Steurer, S. VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy. Int. J. Mol. Sci. 2015, 16, 8591-8606.
Tsourlakis MC, Khosrawi P, Weigand P, Kluth M, Hube-Magg C, Minner S, Koop C, Graefen M, Heinzer H, Wittmer C, Sauter G, Krech T, Wilczak W, Huland H, Simon R, Schlomm T, Steurer S. VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy. International Journal of Molecular Sciences. 2015; 16(4):8591-8606.Chicago/Turabian Style
Tsourlakis, Maria C.; Khosrawi, Puya; Weigand, Philipp; Kluth, Martina; Hube-Magg, Claudia; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Krech, Till; Wilczak, Waldemar; Huland, Hartwig; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan. 2015. "VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy." Int. J. Mol. Sci. 16, no. 4: 8591-8606.