Invasive breast carcinoma - IARC

A
Fig. 1.22 A Classic invasive lobular carcinoma with uniform, single cell files compared to (B). B Invasive pleomorphic lobular carcinoma with characteristic pleomorphic,
atypical nuclei.
B
3235}. ER was found to be expressed in
the classical form and in variants {1994},
but the rate of positivity was higher
(100%) in alveolar {2668} and lower
(10%) in pleomorphic ILC {2318} than in
the classical type. The proliferation rate
in ILC is generally low {2027}. With the
exception of pleomorphic lobular carcinoma
ERBB2 overe x p ression in ILC
{2274,2477,2750}, is lower than reported
in IDC {2358}.
Genetics
Using flow cytometry, ILCs were found
near diploid in about 50% of the cases
{887}. This fits with the finding that chromosomal
abnormalities, assessed by
cytogenetical {887} or comparative
genomic hybridization (CGH) analysis
{2027}, are less numerous in ILC than in
IDC. In ILC, the most common genetic
alteration, found in 63-87% of the cases
{887,2027}, is a loss of the long arm of
chromosome 16.
The E (epithelial)-cadherin gene, which
maps in 16q22, is implicated in maintaining
coherence of adult epithelial
tissues {1217}, and acts as a cell differentiation
and invasion suppressor factor
{922,3030}. A correlation has been found
between deletion of 16q and the loss of
E-cadherin expression {2027}. Immunohistochemical
analysis has shown
complete loss of E-cadherin expression
in 80-100% of ILC {956,1892,2094,
2152,2336}. This contrasts with the
m e re decrease in staining intensity
observed in 30-60% of IDC.
Molecular analysis has shown that, in
most cases, the lack of E-cadherin
immunostaining can be related to the
presence of protein truncation mutations
{260,1394,2380}, together with the inactivation
of the wild type allele. Alternative
mechanisms may also be involved in
the alteration of E-cadherin {723,3190}
and/or of E-cadherin-associated proteins
{723,1892,2337,2374}.
Analysis of neoplastic lesions corre s p o n-
ding to early steps of tumour development
has shown that both loss of hete
rozygosity of the 16q chro m o s o m a l
region {800} and of E-cadherin expre s-
sion {649,3034} were also observed in
LCIS and in mixed ductal-lobular carc i n o-
ma {34}. Inactivation of the E-cadherin
gene may thus re p resent an early event in
oncogenesis and this biological trait indicates
that LCIS is a potential precursor of
ILC. However, other molecular events
must be involved in the transition from
in situ to invasive lobular tumours.
F u rt h e rm o re, genetic losses concern i n g
other parts of the long arm of chro m o-
some 16 than the locus of E-cadherin
have been found in IDC and in ILC {2960},
as well as in DCIS {460}. This stro n g l y
suggests that several genes localized in
this chromosomal region, and pre s e n t i n g
tumour suppressive pro p e rties, may be
involved in breast oncogenesis.
A combination of mutation analysis and
E-cadherin protein expression may offer
a method for identification of lobular
carcinoma.
Prognosis and predictive factors
A lower frequency of axillary nodal
metastasis in ILC than in IDC has been
reported in several series, the difference
ranging from 3-10% {1327,1578,2541,
2696,2935}. Metastatic involvement by
sc a t t e red isolated cells may simulate
sinusoidal histiocytes and re q u i re
immunohistochemical detection.
The metastatic pattern of ILC differs from
that of IDC. A higher frequency of tumour
extension to bone, gastro-intestinal tract,
uterus, meninges, ovary and diff u s e
serosal involvement is observed in ILC
while extension to lung is more frequent
in IDC {319,1142,1327,2541,2696,2935}.
IHC using antibodies raised a g a i n s t
GCDFP-15, cytokeratin 7, ER, and
E-cadherin may help establish a female
genital tract tumour as a metastatic ILC.
Several studies have reported a more
favourable disease outcome for ILC than
for IDC {705,725,771,2696,2935} whereas
others found no significant differences
{2205,2541,2696,2731} or a worse prognosis
for ILC {126}.
When the histological subtypes of ILC
w e re analysed separately, a more
favourable outcome was reported for the
classical type than for variants {699,
705,725}. However, alveolar ILC has
been considered as a low grade tumour
{2668}, whereas a poor prognosis of
pleomorphic ILC has been reported in
some series {808,3082}. No difference in
the outcome of different subtypes has
been observed in other series {2935}.
Furthermore, a large extent of lymph
node involvement has not been found to
increase significantly the risk of local
relapse {2570}. A link between lack of
E-cadherin expression and adverse outcome
of the disease has also been
reported {125,1176}.
Invasive breast cancer
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