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Characterization
of a
novel anti-fatty acid synthase (FASN) antiserum in breast tissue
Mod
Pathol 2008
Dec; 21(12):1413-20.
Jensen KC*,
Schaeffer DF*,
Cheang M*,
Montgomery K*,
West RB*,
Gilks CB*,
Ross D+,
Turashvili G*,
Schnitt S*,
van de Rijn M*.
*Department of
Pathology, Stanford
University
Medical
Center,
Stanford, CA
94305,
USA.
+Applied Genomics Inc, Burlingame,
CA.
Fatty acid
synthase (FASN)
expression has been reported in many different tumors, including breast
cancer.
In gene microarray studies, the fatty acid synthase gene co-clustered
with
cytokeratins 5 and 17 and other genes that defined the basal-like
subset of
breast cancers. To define the use of this marker in breast pathology, a
rabbit
polyclonal antiserum (S143) to a peptide fragment of this gene was
produced and
compared with a commercially available monoclonal antibody by
immunohistochemistry on various tissue microarrays and whole tissue
sections.
The tissue microarrays included 1090 breast cancers and 244 normal
breast
tissues. Whole tissue sections consisted of benign and malignant
tissues from
breast resection specimens. In contrast to other 'basal' markers
identified by
gene expression profiling data, the fatty acid synthase (FASN)
expression
pattern in normal breast was notable for its expression in only a small
subset
of basal and suprabasal cells. Dual staining experiments revealed that
the
subpopulation of cells labeling with FASN did not coexpress
myoepithelial
markers CK5/6 or p63, but did coexpress e-cadherin. In addition to
staining a
subset of basal and suprabasal cells, the antiserum highlighted
apocrine
differentiation, and stained 106/144 (74%) cases of columnar cell
lesions and
five of five cases of flat epithelial atypia. Despite its association
with
basal keratins in gene array studies, FASN expression did not correlate
significantly with the outcome in breast cancer. We describe an
expression
pattern that highlights only a subset of basal and suprabasal cells in
normal
breast ducts and we show by dual expression studies that this subset of
cells
is different from myoepithelial and basal cytokeratin-positive cells.
In
addition, FASN expression is described in apocrine metaplasia, columnar
cell
lesions, and flat epithelial atypia.
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