Article
High expression of Cathepsin E in tissues but not blood of patients with Barrett’s esophagus and adenocarcinoma
Annals of Surgical Oncology
(2014)
Abstract
Background.
Cathepsin E (CTSE), an aspartic proteinase,
is differentially expressed in the metaplasia–dysplasia–
neoplasia sequence of gastric and colon cancer. We eval-
uated CTSE in Barrett’s esophagus (BE) and cancer
because increased CTSE levels are linked to improved
survival in several cancers, and other cathepsins are up-
regulated in BE and esophageal adenocarcinoma (EAC).
Methods.
A total of 273 pretreatment tissues from 199
patients were analyzed [31 normal squamous esophagus (NE),
29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108
EAC]. CTSE relative mRNA expression was measured by
real-time polymerase chain reaction, and protein expression
was measured by immunohistochemistry. CTSE serum levels
were determined by enzyme-linked immunosorbent assay.
Results.
Median CTSE mRNA expression levels were
C
1,000-fold higher in BE/intestinal metaplasia and BE/D
compared to NE. CTSE levels were significantly lower in
EAC compared to BE/intestinal metaplasia and BE/D, but
significantly higher than NE levels. A similar expression
pattern was present in immunohistochemistry, with absent
staining in NE, intense staining in intestinal metaplasia and
dysplasia, and less intense EAC staining. CTSE serum
analysis did not discriminate patient groups. In a uni- and
multivariable Cox proportional hazards model, CTSE
expression was not significantly associated with survival in
patients with EAC, although CTSE expression above the
25th percentile was associated with a 41 % relative risk
reduction for death (hazard ratio 0.59, 95 % confidence
interval 0.27–1.26,
p
=
0.17).
Conclusions.
CTSE mRNA expression is up-regulated
more than any known gene in Barrett intestinal metaplasia
and dysplasia tissues. Protein expression is similarly highly
intense in intestinal metaplasia and dysplasia tissues.
Disciplines
Publication Date
2014
DOI
10.1245/s10434-014-4155-y
Citation Information
Fisher, O., Levert-Mignon, A., Lord, S., Botelho, N., Freeman, A., Thomas, M., Falkenback, D., Wettstein, A., Whiteman, D., Bobryshev, Y., and Lord, R. (2014). High expression of Cathepsin E in tissues but not bloodof patients with Barretts esophagus and adenocarcinoma. Annals of Surgical Oncology, 22(7), 2431-2438. DOI: 10.1245/s10434-014-4155-y