title: VEGFR-1 overexpression identifies a small subgroup of aggressive prostate cancers in patients treated by prostatectomy.
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.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. m.tsourlakis@uke.de.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. puya.khosrawi@hotmail.de.
authors.forename: Puya
authors.initials: P
authors.lastname: Khosrawi
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. philipp.weigand@uke.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Weigand
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. m.kluth@uke.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. c.hube@uke.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. s.minner@uke.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. c.koop@uke.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. graefen@uke.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. hhuland@uke.de.
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. c.wittmer@uke.de.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. g.sauter@uke.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. t.krech@uke.de.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. w.wilczak@uke.de.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. hhuland@uke.de.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. r.simon@uke.de.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. tschlomm@uke.de.|Department of Urology, Section for translational Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. tschlomm@uke.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany. s.steurer@uke.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000517:prevention & control; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D040281:Vascular Endothelial Growth Factor Receptor-1