370
Chapter 11
to 2.216 for comedocarcinoma, but the differences were not
statistically significant.
Bose et al.
101
analyzed periductal angiogenesis using
factor VIII and CD34 immunostains in comedo and non-
comedo types of DCIS. Small capillaries were usually pres-
ent in the connective tissue, but they were sparse in the
region of the basement membrane around normal ducts.
New vessel formation associated with DCIS was limited to
the region of the basement membrane in ducts with DCIS
(Fig. 11.54). Evidence of angiogenesis was found in 80%
of DCIS consisting of a ring of neovascularity completely
or partially encircling the affected duct. A complete ring
was found more often around comedo DCIS, whereas non-
comedo lesions tended to have a partial ring or no periduc-
tal neovascularity (Figs. 11.28 and 11.54). Using a different
method of quantitation, Guidi and Schnitt
166
confirmed
that maximal periductal neovascularity was associated
FIG. 11.52.
DCIS, low grade.
A:
Solid DCIS.
B:
Micropapillary architecture.
A
B
FIG. 11.53.
DCIS, low and high nuclear grade in a single
duct.
with comedocarcinoma, the expression of HER2, and with
a high PI.
Engels et al.
167
compared DCIS with increased stromal
vascularity in between affected ducts, which they termed
“pattern I” and lesions in which neovascularity formed a
dense rim around the basement membrane (“pattern II”).
Patterns I and II were present alone in 11% and 16%, re-
spectively, of 75 cases. Increased vascularity with either pat-
tern alone or in combination was associated with high-grade
forms of DCIS.
The observed pattern of angiogenesis may be related
in part to the fate of myoepithelial cell layer in ducts that
develop DCIS. Myoepithelial cells are more likely to per-
sist in low-grade DCIS, and they are usually markedly at-
tenuated or absent in high-grade or comedo DCIS. It has
been suggested that myoepithelial cells may exert a tumor
suppressor influence on the development or progression
of DCIS.
104,168,169
Several lines of evidence appear to sup-
port this hypothesis.
In vitro
and
in situ
tissue studies
have demonstrated that myoepithelial cells express high
amounts of proteinase inhibitors, including maspin, pro-
tease nexin II, and α
1
-antitrypsin, and that these inhibi-
tory proteins are concentrated in the stroma surrounding
ducts.
170,171
The effect of these inhibitors of matrix metal-
loproteinases is to decrease tumor invasiveness and to re-
duce angiogenesis.
105,170
Angiogenesis associated with DCIS may also be modu-
lated by the ability of the neoplastic cells to express angio-
genic proteins such as the vascular endothelial growth factor
(VEGF). High-grade DCIS and a significantly higher mi-
crovessel count have been associated with stronger VEGF
mRNA expression detected by
in situ
hybridization.
172
Vasohibin-1 is a negative feedback regulator of angiogen-
esis. The status of neovascularization can be determined by
the expression of vasohibin-1 mRNA that was more highly
expressed in higher grade of DCIS in one study
173
; however,
data regarding the degree of angiogenesis in various grades
of DCIS are conflicting.
174
