Angiogenesis is hypothesized to play a critical role in the development and progression of prostate cancer. Quantitative biomarkers of angiogenesis in human prostate cancer that can be employed in studies of etiologic risk factors or in predicting prognosis are needed. In this study, we examined the vascular architecture in cancer and non-cancerous areas within the same prostate gland, among 100 randomly selected men from the Health Professionals Follow-up Study who underwent radical prostatectomy. Histopathologic sections were stained immunohistochemically for the endothelial marker Factor VIII. Within each case, areas of malignancy and sites of non-malignant prostate tissue were identified by digitally imaging (200X) three random, non-overlapping areas. Image analysis (using Image Pro Plus) provided quantitative data regarding the number of vessels (vascular density) and indicators of vascular structure (diameter, perimeter, roundness). Mean vascular density was significantly greater (vascular structures per field, Mean ± SD, P<0.01) within areas of cancer (32 ± 18) than in the surrounding nonmalignant tissue (12 ± 6.0). Vessel morphology was also different. Areas of cancer tended to have vessels that were smaller in size based upon mean vessel area, perimeter, or diameter (diameter of 75 ± 31 \#956;m vs. 318 \#956;m ± 145 for cancer vs. normal, P<0.01) than vessels in the surrounding non-malignant areas. Finally, using image analysis, with a perfect circle defined as a score of 1.0, we observed that prostate cancer vessels were more irregular in shape (score of 2.6 ± 0.4) compared to vessels in non-malignant prostate tissue (score of 2.2 ± 0.4). Together, these observations demonstrate that the vascular architecture within prostate cancer is characterized by a greater number of vessels of smaller size, with a shape that is more irregular. The relationship of vascular architecture to pathologic grade and stage will be presented. Ongoing work within this cohort shows that smaller vessel size and irregular vascular shape in the tumor at the time of prostatectomy, are strong predictors of future lethal prostate cancer. The application of digital image analysis of vascular structure may provide a quantitative biomarker of tumor angiogenesis that has relevance to etiologic factors, may have prognostic significance, or can be used as an indicator of response to therapeutic interventions. Supported by: NIH/NCI P01CA055075; The Ohio State University Comprehensive Cancer Core Grant, NIH/NCI: 5 P30 CA016058.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3188.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO