Two-dimensional neovascular complexity is significantly higher in nontumor prostate tissue than in low-risk prostate cancer

PURPOSE: Prostate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma. MATERIALS AND METHODS: A total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-microm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension. RESULTS: Our results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence. CONCLUSIONS: The value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.

Identificación de factor de crecimiento endotelial vascular (VEGF) en cáncer de próstata / Identification of vascular endotelial growth factor (VEGF) in prostate cancer

El cáncer de próstata (Ca P) es la segunda causa de muerte en hombres y su comportamiento es tan heterogéneo que se ha sido necesario buscar factores pronósticos que sean fiables. Entre ellos, se está investigando la angiogénesis, proceso necesario para el crecimiento y desarrollo de metástasis del cáncer. El factor de crecimiento endotelial vascular (VEGF), es uno de los factores proangiogénicos más potentes encontrados. No se ha llegado a un consenso internacional en cuanto a su validez como factor pronóstico y tampoco hay estudios en Chile que demuestren una diferencia en su presencia entre el cáncer prostático y la hiperplasia benigna prostática (HBP). Se propuso investigar ambas relaciones en nuestro medio pues contamos con la alternativa de efectuar inmunohistoquímica a pesar de nuestras clásicas limitaciones tecnológicas. Se contaron con 66 biopsias obtenidas de cirugía prostática, de las cuales 30 eran prostatectomías radicales por cáncer prostático clínicamente localizado y 36 eran HBP obtenidas por técnica transvesical. Se les realizó inmunohistoquímica para VEGF y se obtuvo el porcentaje de marcaje de células glandulares por paciente. Se encontró una relación estadísticamente significativa en el porcentaje de marcaje entre cáncer yHBP, ya que el marcaje está prácticamente ausente en la HBP. Cuando se intento correlacionar la intensidad del marcaje con la evolución y el pronóstico de los tumores no se encontró relación entre el porcentaje de marcaje y el mal pronóstico de los tumores operados como en el caso de los cánceres que evolucionaron con recidiva bioquímica definida comoPSA mayor de 0,2 ng/ml. Como expectativas de utilidad clínica podemos plantear que en el futuro el VEGF podría tener utilidad en facilitar el diagnóstico de cáncer y un eventual uso como criterio para optar por una terapia antiangiogénica.

Introduction. Prostate cancer (PCa) is the second cause of death in men and its behavior is so versatile that it has been necessary to search for reliable prognostic factors and therapeutical targets, such as angiogenesis. The Vascular Endothelial Growth Factor (VEGF) is one of the most powerful proangiogenic factors. There is no agreement on its validity as a prognostic factor. Material and methods. A case control study was performed in patients with PCa age matched with patients with benign hyperplasia (BPH). Specimens from prostatectomies were studied using immunohistochemical staining of VEGF in prostate gland cells. The percentage of stained glandular cells per patient was calculated, and associated with diagnosis and recurrence. Prostatic Specific Antigen (PSA) over 0.2 ng/ml at 1 year after the surgery was considered as a recurrence. Results. Sixty biopsies were available, obtained by radical prostatectomy, of which 30 were PCa and 30 were BPH. PCa biopsies had a proportion of VEGF stained cells of 79.5 per cent, while BPH had a 0.86 per cent of stained cells (p<0.0001). However, association between staining percentage and recurrence of the PCa was not found. Discussion: Glandular cells in prostatic cancer show a significantly different pattern of VEGF than in non neoplasic prostates. VEGF could be useful to make PCa diagnosis in cases of dubious biopsies, through positive or negative staining for VEGF. Further studies are necessary to evaluate whether VEGF pattern correlates with aggresiveness of prostate cancer.

Contrast-Enhanced Harmonic Ultrasonography for the Assessment of Prostate Cancer Aggressiveness: a Preliminary Study

OBJECTIVE: To determine whether contrast-enhanced harmonic ultrasonography can be used to predict the aggressiveness of prostate cancer. MATERIALS AND METHODS: Contrast-enhanced harmonic ultrasonography was performed in 103 patients suspected of prostate cancer before biopsy. Time intensity curves were reconstructed for systematic biopsy sites and sonographic abnormalities. The characteristics of the curves were described using hemodynamic indices including arrival time (AT), time-to-peak (TTP), and peak intensity (PI). The differences of hemodynamic indices between high-grade and low-grade cancer were analyzed and the correlations between the hemodynamic indices and biopsy Gleason score were studied. RESULTS: Prostate cancer was detected in 41 of 103 patients and there were significant differences in the hemodynamic indices between the biopsy sites of the non-malignant patients and prostate cancer lesions (p < 0.05). The prostate biopsies revealed 154 prostate cancer lesions, including 31 low-grade lesions and 123 high-grade lesions. The hemodynamic indices AT and TTP of high-grade tumors were significantly shorter than those of low-grade tumors (p = 0.001, 0.002). In addition, high-grade peripheral zone (PZ) tumors had higher PI than low-grade PZ tumors (p = 0.009). The PZ prostate cancer Gleason score correlated with PI, AT and TTP, with Spearman correlation coefficients of 0.223, -0.335, and -0.351, respectively (p = 0.013, < 0.001 and < 0.001). CONCLUSION: Contrast-enhanced ultrasound measurements of hemodynamic indices correlate with the prostate cancer Gleason score.