Endoglin (CD105) expression in human renal cell carcinoma

Sandlund, Johanna; Hedberg, Ylva; Bergh, Anders; Grankvist, Kjell; Ljungberg, Börje; Rasmuson, Torgny

doi:10.1111/j.1464-410x.2006.06006.x

Cited by 48 publications

(33 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As expected, we found overexpression of Endoglin protein in the endothelium of colon carcinoma tissue, positively correlated with disease progression. These results are in agreement with studies showing that the CD105 + -MVD value is a prognostic marker in colon carcinoma (41,(48)(49)(50), as well as in prostate (51), breast (52,53), kidney (54), esophageal (55,56), head and neck (57,58), uterus (59) and non-small cell lung cancers (60).…”

Section: Discussionsupporting

confidence: 82%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. The precise timing of the angiogenic switch in colorectal cancer development is still unclear. The simultaneous expression of Endoglin (CD105), transforming growth factor (TGF)-ß1 and TGF-ß receptor (R) II were quantified in surgical specimens comprising normal human colon, pre-malignant dysplastic tissue, in situ, and invasive colon cancer specimens, at mRNA and protein levels, respectively by real-time PCR and immunohistochemistry. Serum concentrations of soluble Endoglin and TGF-ß1 were evaluated. mRNA and CD105 + -microvessel density (MVD) increased significantly in dysplastic colon and carcinoma versus normal tissues; values correlated respectively with dysplasia degree and Dukes' stages. TGF-ß1 expression was significantly upregulated in most severe dysplastic adenoma specimens, while TGF-ß1 transcript and protein signals were intense in carcinoma, positively-correlated with tumor progression. TGF-ß1 RII was overexpressed in adenoma and carcinoma versus normal samples, but unrelated with dysplasia or Dukes' stage. Soluble Endoglin serum levels were equivalent in adenoma and normal tissues; in carcinoma the highest levels were in invasive tumor. Circulating TGF-ß1 levels were increased in severe dysplasia and progressed with tumor progression. Correlations between adenoma dysplasia degree and TGF-ß RII and CD105 + -MVD, and between tumor Dukes' staging and TGF-ß1 and CD105 + -MVD, were significant. TGF-ß1 and Endoglin and TGF-ß1 serum levels, TGF-ß1 staining and CD105 + -MVD were significantly and inversely associated with disease-free survival. TGF-ß1 levels were an independent and significant prognostic factor of disease-free survival. These findings suggest active angiogenesis occurs in many pre-malignant colon cases and supports more careful evaluation of different chemopreventive agents.

show abstract

Section: Discussionsupporting

confidence: 82%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…As summarized in Table 1, higher MVD has been reported in many studies to be a favorable prognostic factor (eg, a higher blood vessel density in CCRCC is correlated with a better prognosis or longer patient survival). 4,[14][15][16][17][18][19][20][21][22] However, other studies have reported opposite results correlating higher MVD with poorer prognosis, [23][24][25][26][27][28] whereas others have been unable to find a significant prognostic role for MVD. [29][30][31][32][33] The controversy could result from many nonmechanistic factors, including sample size, sampling bias, the different blood vessel markers chosen for immunohistochemical (IHC) characterization, the quality of IHC staining, the methods of vasculature quantification, and the methods of interpretation.…”

Section: Differential Analysis Of Tumor Vasculaturementioning

confidence: 56%

Complexity of tumor vasculature in clear cell renal cell carcinoma

Qian

Huang

Wondergem

et al. 2009

Cancer

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC-namely, undifferentiated and differentiated-correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. Clear cell renal cell carcinoma (CCRCC) is a highly vascularized malignancy. As evaluated by 2-phase multidetector computed tomography angiography, CCRCC is found to be able to develop an aberrant capsular vascular supply with outflow through an ovarian vein or testicular vein, 1 although positron emission tomography shows that blood perfusion of the tumor is reduced compared with normal kidney tissues. 2 Our expression profiling study also indicated that the expression level of vascular endothelial growth factor (VEGF; a potent proangiogenesis factor) in CCRCC is 5-fold higher than in other types of kidney

show abstract

“…21,24,26,28,[62][63][64][65][66] Practically, all studies were based on manual counting of vessels within small areas of tumor utilizing either 'hot-spots' 26,30,67 or small tissue microarray cores. 68 Both factors, small tissue sample and manual input have a large potential for errors; it is logical to replace those methods with standardized computer analyses of large areas. Moreover, the inclusion of an internal reference point is easily achieved by the new methodology and can further increase the accuracy of measurements.…”

Section: Discussionmentioning

confidence: 99%

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study

Iakovlev

Gabril

Dubinski

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P ¼ 0.037, Cox P ¼ 0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P ¼ 0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations. KEYWORDS: CD34; image analysis; kidney cancer; microvascular density; renal cell carcinoma; tumor vascularity; VEGF Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of adult kidney cancer.1 Although early diagnosis and treatment of the disease is associated with a favorable prognosis, patients diagnosed at the metastatic stage have abysmal prospects, with only a 9% 5-year survival rate.2 Neoplasms resected at a pre-metastatic stage can also recur, with the greatest risk of recurrence in the first 3-5 years.3 Detecting recurrences early can impact patient outcome since the likelihood of a good response to systemic treatment is greater when the metastatic burden is small. 4 In addition, surgical resection of a single or limited number of metastases can result in longer survival. 5 Furthermore, B3% of patients will develop a second primary renal tumor, either synchronously or metachronously. 6 The strongest validated prognostic factors in RCC are stage (anatomic extent of disease) and nuclear grade.7 Th...

show abstract

Endoglin (CD105) expression in human renal cell carcinoma

Cited by 48 publications

References 34 publications

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Complexity of tumor vasculature in clear cell renal cell carcinoma

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study

Contact Info

Product

Resources

About