374
Chapter 11
The extracellular domain of HER2 can be detected in the
serum of patients with invasive breast carcinoma, and this
finding has been associated with overexpression in the car-
cinoma detected by IHC.
199
Serum analysis for HER2 may
prove to be a useful method for identifying patients with
microinvasive duct carcinoma. Esteva-Lorenzo et al.
200
de-
scribed a patient with elevated serum extracellular domain
of HER2 at the time a breast biopsy demonstrated comedo
DCIS that was immunoreactive for HER2. Reexcision per-
formed because carcinoma involved the initial excision mar-
gin revealed a microinvasive focus. Thereafter, the serum
level of HER2 decreased to normal. No elevation of serum
extracellular domain HER2 was detected by these authors in
specimens from 8 other patients with DCIS, including 3 with
DCIS immunoreactive for HER2, or in 27 patients with be-
nign biopsies. In women with clinically invasive carcinoma,
serial HER2 serum levels during the course of chemotherapy
did not correlate well with the clinical status of the patients.
201
Less than 10% of DCIS have been characterized as having
the basal-like phenotype on the basis of IHC. These uncom-
mon instances of HER2 (−) high-grade DCIS are not readily
actual measurements of nuclear size, Bartkova et al.
187
ob-
served that 94% of DCIS composed of cells with large nuclei
(20 μm) were positive for HER2, whereas no membrane re-
activity was seen in cells with small nuclei (10 μm). Immu-
noreactivity was present in 71% of DCIS with intermediate
nuclear size (15 μm) and in 91% of lesions composed of cells
with mixed nuclear size. In this series, a small number of
papillary and clinging DCIS with large nuclei were immu-
noreactive for HER2. Others have confirmed the finding of
HER2 immunoreactivity in 85% of micropapillary or cling-
ing DCIS with large or pleomorphic nuclei.
196
The neoplastic
Paget cells in the eponymous disease of the nipple, as well as
those of the associated underlying mammary DCIS, are ER
negative and HER2 positive in more than 80% of cases.
197
HER2 immunoreactivity is found more often in DCIS
with aneuploid nuclei than in carcinomas with diploid nu-
clei, an association that correlates well with the reported
relationship of HER2 to nuclear size.
190,194
There is also a
strong association between positive HER2 reactivity and
a high proliferative rate represented by the thymidine and
MIB1 labeling indices.
194,198
FIG. 11.56.
DCIS, HER2.
A:
HER2 membrane immunoreactivity is present in the DCIS extending
into a lobule but not in nonneoplastic epithelial cells.
B:
HER2-positive, solid high-grade DCIS.
C:
HER2-positive micropapillary DCIS with high-grade nuclei and necrosis.
D:
HER2-negative inva-
sive well-differentiated carcinoma (
right
) and HER2-positive solid DCIS (
left
).
