Pathological significance and prognostic role of microvessel density, evaluated using CD31, CD34, and CD105 in prostate cancer patients after radical prostatectomy with neoadjuvant therapy

Abstract

BACKGROUNDNeoadjuvant hormonal therapy (NHT) is performed to improve the outcome in organ-confined prostate cancer. However, there is little information regarding the relationship between angiogenesis and NHT. The aim of this study was to identify a suitable method to evaluate the angiogenic status of tissue, and to determine the prognostic value of this method for biochemical recurrence in patients who had undergone radical prostatectomy after NHT.METHODSWe analyzed 108 formalin-fixed specimens from patients treated by radical prostatectomy. NHT was administered in 48 patients (52.9%) and 60 patients who had a similar Gleason score and pT stage were selected as a non-NHT treated control group. Microvessel density (MVD) was measured using anti-CD31, anti-CD34, and anti-CD105 antibodies. The expressions of vascular endothelial growth factor (VEGF)-A and thrombospondin (TSP)-1 were also evaluated by immunohistochemistry. The prognostic value of CD31-, CD34-, and CD105-MVD for biochemical recurrence was investigated.RESULTSThe mean/SD of CD105-MVD in the NHT group (13.3/4.7) was significantly (P < 0.001) lower than that in the non-NHT group (125.8/7.3). In the NHT group, CD105-MVD was associated with pT stage and it was positively correlated with VEGF-A expression (r = 0.56, P < 0.001) and negatively correlated with TSP-1 expression (r = 0.42, P = 0.003). CD105-MVD was identified as a significant predictor of biochemical recurrence (BCR) in patients treated with NHT (log rank test, P < 0.001). Although CD31- and CD34-MVD were significantly associated with pT stage or Gleason score in non-NHT group, they were not associated with pathological features and BCR in NHT group.CONCLUSIONSOur results indicate that CD105-MVD reflects the angiogenic conditions in prostate cancer tissues treated with NHT. CD105-MVD was also identified as a significant and independent predictor of biochemical recurrence in prostate cancer patients who underwent radical prostatectomy with NHT. Prostate 75:84–91, 2015. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement

“…[42][43][44] In contrast, there are few reports on the clinical significance and pathological roles of MVD measured by CD105-positive vessels in prostate cancer tissues. 45 Interestingly, when prostate cancer tissues were stained with anti-CD105 antibody, large and established mature blood vessels did not stain positive for CD105, even though they clearly stained positive for CD31 and CD34. 45 This finding supports the opinion that CD105 might more precisely reflect the angiogenic status of prostate cancer tissues.…”

“…45 Interestingly, when prostate cancer tissues were stained with anti-CD105 antibody, large and established mature blood vessels did not stain positive for CD105, even though they clearly stained positive for CD31 and CD34. 45 This finding supports the opinion that CD105 might more precisely reflect the angiogenic status of prostate cancer tissues. Several reports on a variety of different cancer tissues also showed similar results among CD31-MVD, CD34-MVD and CD105-MVD.…”

Microvascular density in prostate core biopsy: Prognostic predictors?

“…Stepen proširenosti karcinoma prostate je među najvažnijim faktorima koji određuje prognozu bolesti i u velikoj meri zavisi od stepena angiogeneze. 10,11 Cilj ovog istraživanja je proučavanje gustine mkrocirkulacije u adenokarcinomu prostate u uzorcima tkiva dobijenim iglenom biopsijom (core biopsy).…”

Updated Landscape of the Tumor Microenvironment and Targeting Strategies in an Era of Precision Medicine

“…In clinics, angiogenesis is assessed by microvessel density (MVD), an important prognostic factor for clinical outcomes of multiple tumor types. In prostate cancer, CD105-MVD reflects the angiogenic conditions in patients treated with neoadjuvant hormonal therapy (NHT) and acts as an emerging independent predictor of biochemical recurrence in prostate cancer patients after radical prostatectomy with NHT [14]. In addition, upregulation of pro-angiogenic ligand VEGFA is associated with a worse prognosis in metastatic colorectal, lung and renal cell cancers.…”