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

Saad, Reda S.; Liu, Yulin L.; Nathan, Girija; Celebrezze, James; Medich, David S.; Silverman, Jan F.

doi:10.1038/modpathol.3800034

Cited by 155 publications

(113 citation statements)

References 37 publications

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“…The correlation between microvessel counts and metastatic disease of the colon has been reported. 5,38 These results are in accordance with angiogenesis and lymphangiogenesis being crucial factors in the metastatic process and thus for the progression of a malignant disease.…”

Section: Discussionsupporting

confidence: 69%

“…23 Lymphatic microvessel counts by podoplanin was correlated with lymphovascular invasion in breast cancer. 5 Studies have indicated that D2-40 can be useful in identifying the presence of lymphatic invasion in various malignant neoplasms. 19 D2-40 outlines tumor emboli in lymphatics otherwise indiscernible by H&E, and increases the detection rate of lymphatic invasion by 16% in melanoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…5,[43][44][45][46][47] Some studies have indicated that VEGF expression is an independent prognostic factor in predicting patient prognosis, 5,[43][44][45] while others have reported no such association. 46 Chung et al 47 also showed that VEGF expression was significantly associated with prognosis and hematogenous spread in colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] However, lymphatic spread of cancer cells to lymph nodes is an important early event in the metastasis of carcinomas. 6,7 Nodal metastasis is a key factor in the staging, an important prognostic indicator for outcome, and forms the basis of treatment of human cancer.…”

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confidence: 99%

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Lymphatic microvessel density as prognostic marker in colorectal cancer

et al. 2006

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Lymph node metastases is an important prognostic indicator for disease progression and crucial for therapeutic strategies in the work-up of colorectal carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular endothelial growth factor (VEGF) expression as predictive markers for the risk of lymph node metastasis and their relation to other prognostic parameters in colorectal carcinoma. Resected colorectal carcinomas from 90 patients were examined, including 30 patients without lymph node metastases, 30 with only lymph node metastases, and 30 with liver metastases. Cases were immunostained for CD31, D2-40, and VEGF. Positivity stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at Â 400 field ( ¼ 0.17 mm 2 ). Intensity of staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel density demonstrated significant correlation with CD31 counts (2079 vs 1876/0.17 mm 2 field, Po0.05) and VEGF expression (Po0.01). VEGF was expressed in 61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients, which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90). There was a positive significant correlation of D2-40, CD31 counts, and VEGF expression with the presence of lymphovascular invasion and lymph node metastases (Po0.05). D2-40 lymphatic microvessel density correlated significantly with depth of invasion (pT), positive vascular pedicle lymph nodes and liver metastases (Po0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic significance with positive correlation with lymphovascular invasion, pT, and metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the detection of lymphatic invasion relative to H&E staining and the endothelial marker, CD31.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Lymphatic microvessel density as prognostic marker in colorectal cancer

et al. 2006

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“…We counted the total number of vessels (both blood and lymphatic) using the pan-endothelial marker CD34. 24,25 A monoclonal antibody raised against podoplanin, as described previously 26,27 (kindly provided by Dr Geleff, Department of Pathology, University of Vienna, Austria), and the commercial monoclonal antibody D2-40 (SIG-730, Signet Laboratories, Dedham, MA, USA, dilution 1:40) were used to stain lymphatic vessels in two adjacent sections. Immunohistochemistry was performed using the EnVision System (DAKO, Copenhagen, Denmark), as previously described.…”

Section: Tissue Samplesmentioning

confidence: 99%

Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach

2005

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Tumor lymphatic density is evaluated by means of specific lymphatic endothelium markers, and is a potential predictor of clinically meaningful outcomes. There are many claims on the postulated superiority of some of these markers to identify lymphatics, always in the absence of quantitative data. We therefore compared the diagnostic accuracy of the antibody against podoplanin and the commercially available D2-40, employing Bayesian statistics to account for the absence of a gold standard. We used the pan-endothelial marker CD34 to identify 23 542 distinct blood and lymphatic vessels in sections from 30 formalin-fixed, paraffin-embedded archival tissue blocks of head and neck squamous cell carcinoma specimens. We stained two adjacent sections with podoplanin and D2-40 and identified the continuum of each stained vessel in the sections with a comprehensive method. Overall, 1864 vessels were stained with both markers, 119 only with podoplanin and 391 only with D2-40. Significantly more vessels with intraluminal red blood cells were stained with D2-40 compared to podoplanin (McNemar's Po0.0001). Both antibodies had extremely high specificity (99.7% (95% credible interval (CrI): 99.5-99.9%) and 98.8% (95% CrI: 98.3-99.5%) for podoplanin and D2-40, respectively) and very high sensitivity (92.6% (95% CrI: 86.1-97.9%) and 97.3% (95% CrI: 94.9-99.2%) for podoplanin and D2-40, respectively). Inferences were qualitatively similar when we took into account in the analyses the possibility that the two tests (antibodies) may be correlated. We calculated that 96.3% (95% CrI: 94.2-98.6%) of the vessels stained with podoplanin and 88.9% (95% CrI: 83.9-95.7%) of the vessels stained with D2-40 were truly lymphatics. These numbers were in agreement with the observed number of stained vessels without intraluminal red blood cells. Our results suggest that both antibodies are excellent lymphatic endothelium markers and that there may be little reason to prefer either of them in most settings.

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