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Evaluation of tumor angiogenesis with a second-generation US contrast medium in a rat breast tumor model.

Ko EY, Lee SH, Kim HH, Kim SM, Shin MJ, Kim N, Gong G - Korean J Radiol (2008 May-Jun)

Bottom Line: The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed.The MVD did not correlate with the pathological diagnosis.However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Objective: Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.

Materials and methods: The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.

Results: The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).

Conclusion: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

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Invasive ductal carcinoma induced by intraperitoneal injection of ethyl-N-nitrosourea. Tumor consists of infiltrating cords and tubules in background of atypical ductal hyperplasia. Arrows on right side indicate tumor necrosis (Hematoxylin & Eosin staining, × 100).
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Figure 2: Invasive ductal carcinoma induced by intraperitoneal injection of ethyl-N-nitrosourea. Tumor consists of infiltrating cords and tubules in background of atypical ductal hyperplasia. Arrows on right side indicate tumor necrosis (Hematoxylin & Eosin staining, × 100).

Mentions: The histological diagnoses of the tumors were 11 invasive ductal carcinomas (IDC) and six benign intraductal epithelial proliferations (IP) (Fig. 2). As these tumors were induced by intraperitoneal administration of a carcinogen, the histological features of the rat breast tumors were not the same as those of human breast tumors that naturally develop; even the benign intraductal proliferation consisted of somewhat atypical cells and there were no areas with normal glandular structures due to exposure to the carcinogen. However, the histological diagnoses were based on areas with findings relatively typical of breast tumors. MVD counted in six high-power fields (× 200) varied from 27 to 176 (Fig. 3). MVD did not correlate with the histological diagnosis of the tumors. In addition, the hemodynamic parameters driven from TICs of contrast-enhanced US also did not correlate with the histological diagnosis of the tumor. The histological diagnosis and MVD of each tumor are shown in Table 3.


Evaluation of tumor angiogenesis with a second-generation US contrast medium in a rat breast tumor model.

Ko EY, Lee SH, Kim HH, Kim SM, Shin MJ, Kim N, Gong G - Korean J Radiol (2008 May-Jun)

Invasive ductal carcinoma induced by intraperitoneal injection of ethyl-N-nitrosourea. Tumor consists of infiltrating cords and tubules in background of atypical ductal hyperplasia. Arrows on right side indicate tumor necrosis (Hematoxylin & Eosin staining, × 100).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2627259&req=5

Figure 2: Invasive ductal carcinoma induced by intraperitoneal injection of ethyl-N-nitrosourea. Tumor consists of infiltrating cords and tubules in background of atypical ductal hyperplasia. Arrows on right side indicate tumor necrosis (Hematoxylin & Eosin staining, × 100).
Mentions: The histological diagnoses of the tumors were 11 invasive ductal carcinomas (IDC) and six benign intraductal epithelial proliferations (IP) (Fig. 2). As these tumors were induced by intraperitoneal administration of a carcinogen, the histological features of the rat breast tumors were not the same as those of human breast tumors that naturally develop; even the benign intraductal proliferation consisted of somewhat atypical cells and there were no areas with normal glandular structures due to exposure to the carcinogen. However, the histological diagnoses were based on areas with findings relatively typical of breast tumors. MVD counted in six high-power fields (× 200) varied from 27 to 176 (Fig. 3). MVD did not correlate with the histological diagnosis of the tumors. In addition, the hemodynamic parameters driven from TICs of contrast-enhanced US also did not correlate with the histological diagnosis of the tumor. The histological diagnosis and MVD of each tumor are shown in Table 3.

Bottom Line: The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed.The MVD did not correlate with the pathological diagnosis.However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Objective: Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.

Materials and methods: The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.

Results: The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).

Conclusion: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

Show MeSH
Related in: MedlinePlus