Comparison between 'in vivo' and 'in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model

Wen Fang Cheng, Chien Nan Lee, Chi An Chen, Jan Show Chu, Cheng Che S Kung, Chang Yao Hsieh, Fon Jou Hsieh

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)295-304
出版狀態已發佈 - 1999

ASJC Scopus subject areas

  • 癌症研究
  • 臨床生物化學
  • 聚合物和塑料
  • 病理學與法醫學


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