Ductal Carcinoma
In Situ
383
FIG. 11.65.
DCIS, basement membrane.
A:
The basement
membrane is highlighted by the immunostain for laminin.
B:
Carcinoma cells in a break in the basement membrane.
C:
Carcinoma cells extending through the basement
membrane are in continuitywith the intraductal component.
necrosis. Carcinoma cells have been observed by electron
microscopy protruding through gaps in the basal lamina
when invasion was not apparent by light microscopy.
285
In
such regions, in H&E sections, the neoplastic epithelium ap-
pears to protrude from the duct, coming in contact with the
stroma as it remains connected to the intraductal neoplasm.
This finding often elicits diagnostic uncertainty. It remains
to be determined whether protruding cells detected by elec-
tron microscopy or light microscopy still attached to their
intraductal counterparts are capable of metastatic spread.
Basement membrane integrity at sites of microinvasion
has been investigated by IHC (Fig. 11.65). Barsky et al.
99
detected fragmentation and disruption of basement mem-
branes in areas of microinvasion by employing antibodies
to laminin and type IV collagen (Fig. 11.66). Type IV colla-
gen is degraded by type IV collagenase, a metalloproteinase.
The active enzyme is absent from normal and proliferative
ducts, variably present in comedocarcinoma, and prominent
in invasive carcinoma.
286
These and other observations sug-
gest that the ability of carcinoma cells to form latent type
IV collagenase and convert it to the active form is an im-
portant attribute associated with the invasive phenotype. As
noted earlier in this chapter, myoepithelial cells also appear
to play a significant role in inhibiting invasion by DCIS.
171
One important function of myoepithelial cells is the elabo-
ration of protease inhibitors that appear to counteract the
invasion-promoting effects of metalloproteinases produced
by DCIS cells. Another important function of myoepithelial
cells in this setting is that they serve as a potential mechani-
cal barrier, along with the basement membrane, between in-
traductal epithelial cells and periductal stroma.
The type IV collagenmolecule consists of a number of dis-
tinctive alpha-chain subunits. The cross-linked alpha chains
form a macromolecular network, which is a major structural
component of the basement membrane. Studies using alpha
(IV) chain-specific antibodies and
in situ
hybridization have
shown that the expression of selected alpha chains is depen-
dent on the presence of myoepithelial cells.
287
Discontinuous
or absent expression of type IV collagen alpha-chain sub-
units has been observed in invasive carcinomas.
287,288
The laminin molecule is also composed of cross-linked
subunits designated alpha, beta, and gamma chains. Im-
munohistochemical studies using chain-specific antibodies
revealed discontinuous or absent expression of most sub-
units in invasive carcinomas and no expression of the beta-2
chain.
288
Microinvasion should be distinguished from minimally
invasive carcinoma, a term that refers to invasive lesions less
