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

Allegheny General Hospital, Pittsburgh, Pennsylvania, United States
Modern Pathology (Impact Factor: 6.19). 02/2004; 17(2):197-203. DOI: 10.1038/modpathol.3800034
Source: PubMed


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 x 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 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). 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 (P<0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (P<0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (P<0.01). 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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    • "On the other hand, endoglin, also known as CD105, has been reported to play a key role in the regulation of neoangiogenesis for tumor growth and progression. Results of previous studies also indicated that endoglin acts as a proangiogenic factor in different kinds of cancer [11], but the significance of VASH-1 in neoangiogenesis in NET has not been elucidated. "
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    ABSTRACT: Neuroendocrine tumors (NET) are highly vascularized, but the process of proliferation and maturation of vascular structures during tumor development and progression has remained unknown. We examined the structural alterations of intratumoral blood vessels in human gastroenteropancreatic NET. Microvessel density was evaluated using the endothelial cell markers vasohibin-1, CD31, and endoglin in 135 cases. Double immunohistochemistry staining was performed to localize endothelium and pericytes on the same vessels using the pericyte marker nestin. The ratio of Ki-67/CD31 was significantly correlated with that of vasohibin-1/CD31 positivity (P < 0.001), indicating that the ratio of vasohibin-1/CD31 also reflects the status of neovascularization in NET. This ratio was higher in NET than in its non-neoplastic counterpart (P = 0.10) and tended to increase according to World Health Organization (WHO) grade, although the differences were not statistically significant (P = 0.32). The ratio of vasohibin-1/nestin-positive vessels, representing the maturation of neovessels, was also significantly higher in NET than in its non-neoplastic counterparts (P = 0.003). Among WHO grades, the ratio increased from grade 1 to grade 2 (P = 0.36) and decreased in neuroendocrine carcinoma (P = 0.34). Our results demonstrated that VASH-1/CD31 can be an ideal immunohistochemical marker for characterizing neovascularization in neuroendocrine tumor. The VASH-1/CD31 content increased with WHO grade, and the vessels covered by pericytes decreased in higher grades. These structural changes in the vessels are considered to play an important role in inducing tumor-cell proliferation.
    Full-text · Article · Apr 2014 · Human pathology
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    • "CD105, a type I membrane glycoprotein that is found in endothelial cells, activated macrophages, fibroblasts and smooth muscle cells is a specific and sensitive marker for tumor angiogenesis. Its expression was associated with increased micro-vessel staining and poor prognosis in childhood’s acute lymphoblastic leukemia [31], breast carcinoma [32], colorectal carcinoma [33] and so on. However, whether CD105 is expressed in sarcoma or malignant PT has not been reported until now. "
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    ABSTRACT: Although breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. Malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and search for the presence of cancer stem cells (CSCs) in phyllodes tumors. Paraffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of nonobese diabetic/severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-CSID mice and their ability to undergo differentiation. Immunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/ GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment . Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes. Our findings revealed that malignant phyllodes tumor possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations.
    Full-text · Article · Mar 2014 · Breast cancer research: BCR
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    • "CD105 expression has been detected by immunohistochemistry for the evaluation of angiogenesis in premalignant and malignant lesions. It is considered more neoangiogenesis-specific than pan-endothelial CD34 and CD31 antibodies and might have a more significant prognostic value for some cancers [14,17,18]. The role of angiogenesis in chronic liver disease, liver premalignant lesions and liver cancer has also been studied using pan-endothelial antibodies [19]. "
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    ABSTRACT: Angiogenesis is a proliferative process resulting in the development of new blood vessels from existing endothelial cells and is considered crucial for tumor growth and metastasis. Tumor angiogenesis can be quantified by microvascular density (MVD), which is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using CD34 and CD31 pan-endothelial antibodies. More recently, CD105 has been successfully used for some tumor types because it could discriminate neovascularization. The expression of CD34 and CD105 in hepatocellular carcinomas (HCC) and hepatic precancerous lesions has been reported--although the results for CD105 are controversial--but to the best our knowledge, CD105 has not been previously investigated in dysplastic nodules (DN). We investigated and compared MVD-CD34 and MVD-CD105 immunoexpression in tissues containing different stages of hepatocarcinogenesis, including DN. A total of 31 regenerative nodules (RN), 26 DN and 25 small HCC from explants were used for immunohistochemical tests with CD34 and CD105 antibodies. Antibody expression was quantified by computerized image analysis measurement of MVD, areas containing highly positive endothelial cells within the nodules. The median MVD for CD34 was higher in HCC than in DN and RN (p < 0.01), and was higher in DN compared with RN (p = 0.033). In contrast, MVD with CD105 was higher in RN, and the difference was significant in RN and DN compared with HCC (p = 0.019 and p = 0.012, respectively). When MVD with CD34 and CD105 were compared within a single group, there was a significant predominance of CD105 in RN and DN (p < 0.01). In addition, MVD-C34 in HCC predominated compared with MVD-CD105, but the difference was not statistically significant (p = 0.128). This study identified a close relationship between CD105 and liver cirrhosis, and that CD34 antibody is a good endothelial marker for hepatic carcinogenesis. There was no difference between the use of CD105 and CD34 antibodies in preneoplastic lesions.
    Full-text · Article · Feb 2014 · BMC Cancer
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