Endoglin (CD105) and vascular endothelial
growth factor as prognostic markers in
Reda S Saad1, Yulin L Liu2, Girija Nathan2, James Celebrezze3, David Medich3and
Jan F Silverman2
1Department of Pathology, Louisiana State University Health Science Center, New Orleans, LA, USA;
2Department of Pathology and3Department of Surgery, Allegheny General Hospital, Pittsburgh, PA, USA
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 ?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 1978/0.15mm2field, 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.
Modern Pathology (2004) 17, 197–203, advance online publication, 5 December 2003; doi:10.1038/modpathol.3800034
Keywords: endoglin; cancer colon; CD31; angiogenesis
In colorectal cancer patients, conventional prognos-
tic parameters such as tumor grade, depth of
penetration, angiolymphatic invasion and lymph
node involvement are important prognostic fac-
tors.1–4However, these histopathologic characteris-
tics do not always predict the outcome for any
individual patients, prompting the need for addi-
tional prognostic markers that can predict the
outcome for these patients more accurately.
Tumor angiogenesis, the formation of peritumor
and intratumor new blood vessels, is necessary to
the growth and metastasis of solid tumors, and is
regarded as one of the most important events occu-
rring in the neoplastic process.3,5Neovasculariza-
tion allows tumor growth by supplying nutrient and
oxygen, disposing metabolites and releasing growth
factors that promote tumor cell proliferation.6Neo-
plasms promote angiogenesis by secreting growth
factors such as vascular endothelial growth factor
(VEGF), hepatocytes growth factor and platelet-
derived growth factor that stimulate endothelial migra-
tion and proliferation.7,8Angiogenesis also contributes
to the metastatic process by providing large numbers
of leaking blood vessels for vascular invasion.7
Recently, there is growing evidence supporting
microvessel density as an important predictor of
tumor behavior in a number of human malignan-
cies.9–16The role of angiogenesis in colorectal
tumors has also been investigated, but the literature
shows contradictory results. While Bossi et al17and
Pietra et al18reported that angiogenesis did not
provide any significant prognostic information for
colorectal cancer patients, Saclarides et al19and
Received 8 May 2003; revised 15 September 2003; accepted 23
September 2003; published online 5 December 2003
Correspondence: R Saad, Department of Pathology, Louisiana
State University Health Science Center, School of Medicine, 1901
Perdido Street, P5-1, New Orleans, LA 70112, USA.
Modern Pathology (2004) 17, 197–203
& 2004 USCAP , Inc All rights reserved 0893-3952/04 $25.00
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