Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development

Akagi, Kazunari; Ikeda, Yoichi; Sumiyoshi, Yoshihiro; Kimura, Yasue; Kinoshita, Jin H.; Miyazaki, Michihiko; Abe, Toru

doi:10.1067/msy.2002.119361

Cited by 81 publications

(72 citation statements)

References 21 publications

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“…Endoglin stained small vessels with high sensitivity in or around the tumor, but the blood vessels in nonneoplastic tissue did not or only weakly stained with endoglin. This is in agreement with previous studies where endoglin was expressed mainly in proliferating blood vessels, while CD34 or CD31 stained all the blood vessels, 21,22,24,31 suggesting that endoglin is preferentially expressed in vessels undergoing neoangiogenesis. Endoglin is very selective for the blood vessel endothelium and reacts specifically with endothelial cells without significant staining of inflammatory or stromal cells within the neoplasm.…”

Section: Discussionsupporting

confidence: 82%

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

et al. 2003

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Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at Â 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31710 vs 1978/0.15 mm 2 field, Po0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (Po0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (Po0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (Po0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.

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Section: Discussionsupporting

confidence: 82%

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

et al. 2003

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“…In contrast, MVD identified by CD34 (and other pan-endothelial markers) may not be able to accurately characterise angiogenesis of certain types of tumour, leading to a lack of association of MVD with tumour progression. This speculation is supported by a recent study by Akagi et al (2002), who have reported that a significant increase of MVD determined by Mab to CD105 but not Mab to CD34 was observed from low-grade to high-grade dysplasia of colorectal mucosa, and from high-grade dysplasia to colorectal carcinoma. In conclusion, the ability to quantitatively discriminate between angiogenesis and pre-existing vessels in tumours seems to be an important determinant in the assessment of tumour angiogenesis.…”

Section: Discussionsupporting

confidence: 57%

“…To obtain MVD data, invariably, previous studies have used pan-endothelial antibodies, for example, against von Willebrand factor, CD31 or CD34, which although ideal for staining normal blood vessels, in our experience are inefficient in recognising angiogenic EC. In contrast, CD105 (endoglin) is abundantly expressed in angiogenic EC, and antibodies to it preferentially bind to EC of angiogenic tissues (Krupinski et al, 1994;Wang et al, 1994;Burrows et al, 1995;Bodey et al, 1998;Kumar et al, 1999;Brewer et al, 2000;Fonsatti et al, 2001;Akagi et al, 2002). Our hypothesis is that this selective immunostaining by an antibody to CD105, that is, its ability to distinguish tumour-associated EC and pre-existing vessels, will reduce the incidence of false-positive staining of normal entrapped vasculature in a cancerous mass (Thompson et al, 1987).…”

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confidence: 99%

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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CD105 and its ligand transforming growth factor b (TGFb) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40 -9.00) and 3.10 (range 0.90 -8.00), respectively. Kaplan -Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFb1 and TGFb3 together with the receptor -ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFb1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFb1 level was noted in patients with carcinoma over the controls. Furthermore, TGFb3 and CD105/ TGFb3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFb1 was expressed in cancer cells but TGFb3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFb1, TGFb3 and CD105/TGFb complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

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“…Thus, endoglin appears to be a highly sensitive angiogenic marker in several malignancies. 13,[22][23][24]31 Several factors may be invoked to explain the endoglin staining pattern seen in the present study and not reported in TUR specimens. While this includes tissue processing, methodology, and analysis of different areas (normal/benign, PIN and cancer), the types of surgical specimens (whole-mount vs TUR) is likely in cause.…”

Section: Discussionmentioning

confidence: 95%

“…Such as superiority of endoglin over vWF but also CD31 and CD34 was reported in other tumors. 22,23,31 In TUR specimens, there was approximately 4-fold lower number of endoglin-vs vWF-stained tumor vessels. 13 Whether this discrepancy is due to differences in methods, cases, and use of whole mount vs TUR sections is unknown, but in both series, endoglinstained tumor microvessels (and vWF in the present series) correlated with Gleason score.…”

Section: Discussionmentioning

confidence: 99%

Whole-mount prostate sections reveal differential endoglin expression in stromal, epithelial, and endothelial cells with the development of prostate cancer

Kassouf

Ismail

Aprikian

et al. 2004

Prostate Cancer Prostatic Dis

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Endoglin is a nonsignaling receptor for transforming growth factor that contributes to the action of this growth factor in diverse cell types. It may also exhibit a function of its own. Endoglin levels vary with disease states and is a marker of new blood vessels. We studied endoglin expression in whole-mount prostate sections from 64 patients with localized prostate cancer, assessing reactivity in the epithelium, the stroma, and blood vessels. Cells in normal/benign acini were negative but significantly immunoreactive (Po0.001) in both prostatic intraepithelial neoplasia (PIN; 52% of cases) and malignant areas (77% of cases). In tumors, this involved less than 25% of malignant cells in 59% of specimens. The endoglin-stained stroma was detected mainly in areas surrounding PIN acini and tumors. Endoglin antibodies detected more microvessels than von Willebrand Factor antibodies in all prostatic areas (Po0.01). In addition, the number of microvessels increased with the development of cancer and correlated with Gleason score (Po0.01). Changes in endoglin expression in PIN and malignant cells, the surrounding stroma, and related blood vessels, suggest that endoglin function may be altered in prostate cancer.

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Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development

Cited by 81 publications

References 21 publications

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Whole-mount prostate sections reveal differential endoglin expression in stromal, epithelial, and endothelial cells with the development of prostate cancer

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