VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy

International Journal of Molecular Sciences

Maria Christina Tsourlakis¹  Puya Khosrawi¹  Philipp Weigand¹  Martina Kluth¹  Claudia Hube-Magg¹  Sarah Minner¹  Christina Koop¹  Markus Graefen²  Hans Heinzer²  Corinna Wittmer¹  Guido Sauter¹  Till Krech¹  Waldemar Wilczak¹  Hartwig Huland²  Ronald Simon¹  Thorsten Schlomm²  Stefan Steurer¹ 

[1]Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany

[2] E-Mails:

[3]Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-210246 Hamburg, Germany

[4] E-Mails:

关键词: VEGFR-1;    TMPRSS2:ERG;    PTEN;    TMA;    prostate cancer;   

DOI  :  10.3390/ijms16048591

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.