Am J Clin Pathol 2007;127:572-579
© American Society for Clinical Pathology
Anatomic Pathology / ENDOGLIN MICROVESSEL DENSITY IN PROSTATIC CARCINOMA
Endoglin (CD105) and Vascular Endothelial Growth Factor
as Prognostic Markers in Prostatic Adenocarcinoma
Yasser M. El-Gohary, MD,1Jan F. Silverman, MD,2Peter R. Olson, MD,2Yulin L. Liu, MD, PhD,2
Jeffrey K. Cohen, MD,3Ralph Miller, MD,3and Reda S. Saad, MD, PhD2
Key Words: Endoglin; Microvessel density; Prostatic carcinoma; Vascular endothelial growth factor; VEGF; CD31
A b s t r a c t
We studied endoglin and vascular endothelial
growth factor (VEGF) expression as prognostic
markers in prostatic adenocarcinoma in 50 radical
prostatectomy specimens. Cases were further
categorized by Gleason score as follows: 8 to 10, 9
cases; 7 (4 + 3), 9 cases; 7 (3 + 4), 14 cases; 6, 13
cases; and 4 or 5, 5 cases. All cases were
immunostained for endoglin, CD31, and VEGF.
Positively stained microvessels were counted in densely
vascular foci in a ×400 field. VEGF staining intensity
was scored on a 2-tiered scale. Results were correlated
with survival and other parameters. Endoglin
demonstrated significantly more microvessels than did
CD31 (mean ± SD, 37 ± 15 vs 22 ± 17; P < .001).
VEGF expression was low in 21 cases (42%) and high
in 29 (58%). Endoglin correlated positively with
Gleason score, lymph node metastases, tumor stage,
and preoperative prostate-specific antigen level (P <
.05) but not with CD31. VEGF correlated significantly
with angiolymphatic invasion and Gleason score (P <
.05). A high endoglin microvessel count and VEGF
expression correlated with shorter survival. Endoglin is
a more specific and sensitive marker for tumor
angiogenesis than CD31 and may serve as a prognostic
marker for prostatic adenocarcinoma.
Adenocarcinoma of the prostate is the most common can-
cer affecting men in the United States.1The incidence of
prostate carcinoma increases directly with age; however, it
causes death in a relatively small proportion of men.1,2Yet, a
subpopulation of prostatic cancers may behave aggressively.1
The development of prognostic markers that can accurately
predict outcome is crucial to identify patients who could ben-
efit from aggressive therapy.
Angiogenesis is a fundamental process by which new blood
vessels are formed, and it is essential for tumor growth by provid-
ing nutrients and eliminating metabolic waste products.3,4
Studies have shown that the tumor neovessels have an aberrant
structure.5Angiogenic vessels show fenestrated capillaries and
thinnerbasement membranes than normal vessels. These changes
will result in increased permeability and provide a route of exit
to tumor cells into the circulation, promoting metastases.6
Angiogenesis has been proposed as a promising prognostic
marker in a variety of tumors.7,8Some studies have investigated
the significance of angiogenesis in prostate carcinoma, with
inconsistent results.9-22Although some studies found that angio-
genesis is associated with tumor stage, Gleason score, or both,
others failed to confirm such findings.14-22In these studies, vas-
cular densities were determined using pan-endothelial markers,
such as von Willebrand factor (factor VIII–related antigen),
CD31, or CD34. Studies in other tumors have suggested that
none of these pan-endothelial cell markers is ideal for tumor
angiogenesis evaluation because they do not stain the newly
formed microvessels and are not specific for endothelial cells.23,24
Endoglin (CD105), a receptor for transforming growth
factor β1, is highly expressed on endothelial cells during
tumor angiogenesis and inflammation with weak or negative
expression in vascular endothelium of normal tissues.25
Am J Clin Pathol 2007;127:572-579 579
© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
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