33 Special Types of Invasive Breast Carcinoma: Diagnostic Criteria ...

pathologic findings indistinguishable from those of metastatic gastric carcinoma
(32,34,37,38). A positive immunohistochemical stain for hormone receptors suggests
metastatic breast carcinoma, but it is not specific. A better stain is GCDFP-15, which
is more specific for breast carcinoma, especially if signet-ring cells are present (36).
Invasive lobular carcinomas commonly express Bcl-2, a protein that plays a pivotal
role in overriding programmed cell death (apoptosis) and, thus, favors a prolonged
survival of normal and neoplastic cells. Doglioni et al. (39) recently investigated the
expression of Bcl-2 in 212 breast carcinomas using the monoclonal antibody 124 and
correlated it with the estrogen (ER), progesterone (PR) and epidermal growth factor
receptor (EGFR) status, and with other clinicopathological variables, including tumor
type, grade, stage, growth fraction (as evaluated by Ki-67 immunostaining and p53
accumulation). Of the 212 carcinomas, 173 (81.6%) exhibited Bcl-2 immunoreactivity
in more than 25% of the neoplastic cells. Bcl-2 immunoreactivity was strongly
correlated with ER and PR expression (P 0.00001), with lobular variant (P = 0.012)
and with better differentiated neoplasms (P = 0.00003), whereas it inversely correlated
with EGFR (P 0.00001), p53 (P = 0.0004) and Ki-67 (P = 0.0002) immunoreactivities.
No association was found with tumor stage (T and N categories). They concluded that
Bcl-2 expression in breast cancers is related to the estrogen-dependent transcription
pathway. Also, Bcl-2 is expressed more commonly in well-differentiated breast
carcinomas (40).
The cell-cell adhesion molecular E-cadherin (E-CD) has been implicated as a
suppressor substance for invasiveness, and it appears to be weakly expressed or absent
in invasive lobular carcinoma. There is also loss of α-, β-, and γ catenins in invasive
lobular carcinoma (60).
Gamallo et al. (41) studied intensity and extension of E-CD immunoreactivity in 61
breast carcinomas and correlated these findings with their histological type and grade,
nodal involvement, and hormonal receptor status. Histological types were infiltrating
ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7).
All infiltrating ductal carcinomas of no special type, except two grade 3 carcinomas,
had varying degrees of positive immunoreactivity. Grade 1 breast carcinomas (n = 10)
showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19)
carcinomas. E-CD immunoreactivity correlated positively with the degree of tubule
formation and inversely with the number of mitoses. In this study, none of the
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