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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)295-304
Number of pages10
JournalAngiogenesis
Volume3
Issue number4
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Microvessels
Tumors
Carcinoma
Neoplasms
Cytosol
Lymph Nodes
Neoplasm Metastasis
Ultrasonics
Immunohistochemistry
Dissection
Doppler Ultrasonography
In Vitro Techniques
Intercellular Signaling Peptides and Proteins
Lymph Node Excision
Hysterectomy
Immunoenzyme Techniques
ROC Curve
Carcinogenesis
Image processing

Keywords

  • Angiogenesis
  • Cervical carcinoma
  • Microvessel density
  • Power Doppler ultrasound
  • Vascular endothelial growth factor
  • Vascularity index

ASJC Scopus subject areas

  • Cancer Research
  • Clinical Biochemistry
  • Polymers and Plastics
  • Pathology and Forensic Medicine

Cite this

Cheng, W. F., Lee, C. N., Chen, C. A., Chu, J. S., Kung, C. C. S., Hsieh, C. Y., & Hsieh, F. J. (1999). Comparison between 'in vivo' and 'in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model. Angiogenesis, 3(4), 295-304.

Comparison between 'in vivo' and 'in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model. / Cheng, Wen Fang; Lee, Chien Nan; Chen, Chi An; Chu, Jan Show; Kung, Cheng Che S; Hsieh, Chang Yao; Hsieh, Fon Jou.

In: Angiogenesis, Vol. 3, No. 4, 1999, p. 295-304.

Research output: Contribution to journalArticle

Cheng, WF, Lee, CN, Chen, CA, Chu, JS, Kung, CCS, Hsieh, CY & Hsieh, FJ 1999, 'Comparison between 'in vivo' and 'in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model', Angiogenesis, vol. 3, no. 4, pp. 295-304.
Cheng, Wen Fang ; Lee, Chien Nan ; Chen, Chi An ; Chu, Jan Show ; Kung, Cheng Che S ; Hsieh, Chang Yao ; Hsieh, Fon Jou. / Comparison between 'in vivo' and 'in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model. In: Angiogenesis. 1999 ; Vol. 3, No. 4. pp. 295-304.
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AU - Cheng, Wen Fang

AU - Lee, Chien Nan

AU - Chen, Chi An

AU - Chu, Jan Show

AU - Kung, Cheng Che S

AU - Hsieh, Chang Yao

AU - Hsieh, Fon Jou

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N2 - 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.

AB - 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.

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KW - Cervical carcinoma

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