Breast cancer is the most common cause of malignant
pleural effusions in women, followed closely by lung
adenocarcinoma. Approximately half of the patients with
disseminated breast cancer develop a malignant pleural effusion
at some time during their illness, while the most
common tumor to initially manifest as a malignant pleural
effusion is lung carcinoma[
11]. As with nodal and soft
tissue metastases, the determination of the primary tumor
site in cases of malignant effusion can be facilitated by
immunoreactivity by various markers. In tissue sections,
the identification of metastatic breast carcinoma has been
greatly enhanced by the use of antibodies directed against
ER and PR, which have been demonstrated to be useful
markers for breast carcinoma[
12].
Immunohistochemistry is proven to be useful in the diagnosis,
classification and prognostication of neoplasms,
making it an ideal tool for the study of effusions, especially
in difficult cases. CA 15-3 is an antigen localized at
the luminal aspect of breast epithelium. It has been used as
a serum marker of occult and recurrent breast carcinoma[7,8]. It has also been used in numerous studies to help
diagnose malignant pleural effusions[9].
Since the early 1990s, antibodies against CA 15-3 have
been developed as possible serum markers of occult or recurrent breast carcinoma[7,8]. Similarly, CA 15-3 has
been examined as a serologic test for breast carcinoma in
pleural fluid[9]. Histologic studies have centered on the
specificity of CA 15-3 for breast carcinoma in metastatic
carcinomas or its sensitivity for detecting micrometastases
in axillary lymph nodes[13,14]. These reports indicate
that CA 15-3 is sensitive, but not specific, for breast carcinoma.
To our knowledge, no recently published work has
examined CA 15-3 as an immunochemical stain to detect
carcinoma in body cavity effusions, although Szpak and
coworkers[15] used their own clone to the DF3 epitope of
CA 15-3 for this purpose in 1984. Given its high sensitivity
for carcinomas, we evaluated a second generation CA
15-3 for its utility to detect breast carcinoma in pleural
effusions.
In this study we have confirmed that CA 15-3 is a
sensitive tumor marker for breast carcinoma, with a sensitivity
of 94%, while Huang et al.[16] and Geraghty and
coworkers[17] have reported 91% and 88% for the sensitivity
of CA 15-3, respectively. Fehm et al.[18] found that
positivity rate of CA 15-3 serum levels was 51% in metastatic
breast cancer. Zimmerman et al.[19] reported that
CA 15-3 was an immunostain with high specificity and
sensitivity for breast carcinoma cases (97%) in cell block
material from effusions. In conclusion, CA 15-3 shows
remarkable potential in diagnosing metastatic breast carcinoma
in cytologic specimens.
It is well recognized that serial radiologic studies,
including bone scans, ultrasonography, and plain radiographs,
are of limited value in the detection of occult metastatic
breast carcinoma. Measurement of tumor marker
levels is an attractive alternative screening technique for
metastatic breast carcinoma, because it is noninvasive,
inexpensive and relatively simple to perform. Carcinoembryonic
antigen is the most widely used marker in monitoring
the development and clinical course of patients with
metastatic breast carcinoma[20]. The poor sensitivity of
this marker, however, limits its usefulness, because only
40-70% of patients with metastatic breast carcinoma have
increased levels[21-24]. CA 15-3 is more specific for
breast cancer and is also more sensitive in patients with
advanced disease[25].
Hormone receptors and c-erbB-2 are established molecular
prognostic markers in breast cancer[26,27]. They are often targeted with therapeutic intention in both localized
and metastatic breast cancer, including in the presence
of malignant effusion. Davidson and coworkers[28]
reported that significantly reduced ER and PR expression
was seen in effusions compared with primary tumors, with
opposite findings for c-erbB-2 which was highest in effusions
and lower expression in primary tumors.
Ali et al.[29] and other investigators have reported increased
soluble c-erbB-2 in the plasma or serum of 20-30%
of patients with metastatic breast cancer[30-32]. Bozzetti
et al.[33] reported that c-erbB-2 status was mostly stable
in primary breast carcinoma and in the corresponding
distant metastatic sites on cytologic material. We reported
that 21% of breast carcinomas cases showed positive
staining for c-erbB-2 in this paper. Lee et al.[34] evaluated
the hormonal receptors for ER and PR for cytology
cell block preparations from 96 effusion specimens. They
reported that 21 (72%) were reactive for ER, 15 (52%) for
PR, and 13 (45%) for both receptors. They suggested that
the detection of ER and PR in metastatic adenocarcinoma
from pleural effusions could distinguish breast from lung
primary sites. Several studies have shown that metastatic
breast cancer patients with a high disease burden have a
poorer prognosis[35,36]. It is difficult to quantify disease
burden with imaging studies, and some patients have
evaluable but not measurable disease. Pleural effusion CA
15-3 is used as a surrogate marker of disease bulk to monitor
metastatic breast cancer patients undergoing treatment
and for the preclinical detection of tumor recurrence. One
report has shown that increased HER-2/neu is associated
with both decreased response rate and shorter time of survival[37].
In this study, we evaluated c-erbB-2 status on metastases
from breast carcinoma patients performed on cytologic
material. Since the advent of trastuzumab, the characterization
of the molecular profile in metastatic disease has become
increasingly important for targeted therapy selection.
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