Microvessel Density Is Not Increased in Prostate Cancer: Digital Imaging of Tissue Microarray and Routine Sections
Tatjana Antic, David Binder, Masha Kocherginsky, Chuanhong Liao, Jerome Taxy, Aytek Oto, Maria Tretiakova. University of Chicago, Chicago
Background: Angiogenesis is considered a therapy target in many tumor systems including prostate cancer (PC). It is reported that there is increased vascularity in PC compared to normal prostate; however, this is not universally accepted. This study compares the microvessel density (MVD) of PC and normal prostate tissue using an automated approach to determine if MVD is a useful prognostic indicator and possible treatment target in PC.
Design: Tumor and normal prostatic tissue from 136 radical prostatectomy specimens was used to create tissue microarrays (TMA); an additional 60 radical prostatectomies were examined by routine histological sections. MVD was calculated by using CD31 immunohistochemical stain in ten 100X representative fields from tumor and normal tissue on routine sections, and in three to six 1.5 mm TMA cores. ACIS and Aperio automated systems were used to digitally analyze MVD in routine sections and TMA cores respectively. Wilcoxon signed rank test was used to compare MVD values in routine sections. In TMAs, a mixed effects model was used to account for multiple cores per patient.
Results: MVD was not significantly increased in tumors vs. normal prostate tissue in routine sections (p=0.269), and was lower in tumors in the TMAs (p=0.024). Both the vessel count and vessel area were higher in normal than in tumor in routine sections by ACIS analysis (p<0.001). Aperio analysis additionally showed significantly higher values in normal tissue for vessel area (p=0.009) and lumen (p<0.001), whereas vessel perimeter and wall thickness were not significantly different (p=0.06 and p=0.25, respectively). Comparison of low grade (n=168 cores) vs. high grade PC (n=30 cores) on TMA showed no significant difference between MVD (p=0.05), vessel area (p=0.88), perimeter (p=0.91), lumen (p=0.21) or wall thickness (p=0.93).
Conclusions: The results, using two different approaches, show that MVD is not increased in PC compared to normal prostate. By calculating MVD from representative fields instead of vascular "hotspots" and using automated quantitation, we attempted to eliminate sources of bias possibly contributing to previous contradictory results. Similar MVD of low and high grade tumors indicate that MVD is neither an important nor reliable prognostic indicator for PC, and that antiangiogenesis drugs might not be of value.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 114, Tuesday Afternoon