Comparison between `in vivo' and `in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model |
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Authors: | Wen-Fang Cheng Chien-Nan Lee Chi-An Chen Jan-Show Chu Cheng-Che S Kung Chang-Yao Hsieh Fon-Jou Hsieh |
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Institution: | (1) Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan;(2) Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan |
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Abstract: | The role of angiogenesis in tumorigenesis is widely accepted. Therefore, it is mandatory to develop a clinically useful method
for assessing tumor angiogenesis. This study was designed to compare the `in vivo' and `in vitro' methods for assessing angiogenesis and to evaluate their clinical application using cervical carcinoma as a model. Ninety
women with stages IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were enrolled in
this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Vascularity index (VI)
was assessed by power Doppler ultrasound and a quantitative image processing system. The microvessel density (MVD) of the
excised tumors was immunohistochemically assessed. Both the enzyme immunoassay and immunohistochemistry methods were performed
for assessing the protein levels of vascular endothelial growth factor (VEGF) in tumor tissues. Significantly higher VI, MVD
and cytosol VEGF concentrations were detected in tumors with deep stromal invasion (≥1/2 thickness) (11.43 ± 7.25 vs. 5.87
± 6.81, P < 0.001; 53.0 vs. 37.0, P = 0.006, 550.0 vs. 86.0 pg/mg, P < 0.001), lymphatic invasion (12.21 ± 7.89 vs. 6.86 ± 6.29, P < 0.001; 53.0 vs. 40.0, P = 0.038; 930.0 vs. 110.0 pg/mg, P = 0.002), and pelvic lymph node metastasis (17.15 ± 8.58 vs. 7.83 ± 6.41, P < 0.001; 54.0 vs. 39.0, P = 0.02; 964.0 vs. 131.0 pg/mg, P = 0.002). VEGF-rich tumors detected by immunohistochemistry also revealed higher VI (12.26 ± 7.96 vs. 8.05 ± 7.62, P = 0.012), MVD (53.0 vs. 37.5, P = 0.01) and cytosol VEGF levels (745.0 vs. 98.0 pg/mg, P = 0.002). The relationships between VI values, MVD values and cytosol VEGF concentrations were linear (VI vs. MVD, r = 0.38, P < 0.001; VI vs. VEGF, r = 0.78, P < 0.001; MVD vs. VEGF, r = 0.29, P = 0.006). As revealed by the receiver operating characteristic (ROC) curve analysis, VI is better than MVD and VEGF in predicting
lymph node metastasis. In conclusion, there is histological, molecular and clinical evidence supporting VI as a useful `in vivo' indicator of tumor angiogenesis, particularly for predicting lymph node metastases in cervical carcinomas.
This revised version was published online in June 2006 with corrections to the Cover Date. |
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Keywords: | angiogenesis cervical carcinoma microvessel density power Doppler ultrasound vascular endothelial growth factor vascularity index |
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