21 / 366
In addition to cytoplasmic and canalicular, ORF2 protein also revealed a
hitherto not described nuclear localisation. HEV RNA detection by ISH in
defined areas correlated with positivity for ORF2 protein. IHC was specific
and comparably sensitive as PCR for HEV RNA.
Conclusion:
In livers from patients with hepatitis E, the ORF2 protein
can be reliably visualized, allowing sensitive and specific detection of
HEV in FFPE samples. Furthermore, its variable subcellular distribution
in individual hepatocytes of the same liver might provide the basis for an
interaction with nuclear components, and argues for a redistribution of
ORF2 protein during infection.
OFP-02-010
Increased 53-binding protein 1 nuclear foci expression in the liver of
patients with non-alcoholic fatty liver disease
Y. Akazawa
*
, R. Nakashima, K. Matsuda, K. Nakao, M. Nakashima
*
Nagasaki University Hospital, Pathology, Japan
Objective:
NA damage response (DDR) results in genomic instability,
leading to transformation to cancer. However, presence of DDR in non-
alcoholic fatty liver disease (NAFLD) is largely uninvestigated. We
aimed to investigate the expression of 53BP-1 binding protein (53BP1),
a DDR molecule that forms foci upon DNA double-strand breaks, in
NAFLD.
Method:
Forty paraffin-embedded human liver biopsy samples including
five from normal livers, 10 from simple steatotic livers, and 25 from livers
with non-alcoholic steatohepatitis (NASH) were studied by co-
immunofluorescence with the anti-53BP1 and hepatocyte marker.
Nuclear foci more than 2 were considered abnormal expression.
Expression of 53BP1 was then compared with pathological features.
Results:
The number of 53BP1 abnormal nuclear foci was significantly
increased in the hepatocytes of NASH livers (30 %) and simple steatotic
livers (20.1 %) compared to normal control (1.9 %). Expression of 53BP1
foci co-localized with that of histone 2AX, confirming the presence of
DDR. The degree of 53BP1 abnormal expression was not significantly
associated with NAS overall score but had positive correlation with lob-
ular inflammation.
Conclusion:
Our study suggests increased genomic instability in
NAFLD liver, even when the routine pathological examination shows
steatosis without NASH. Our finding may benefit the risk management
of carcinoma occurrence in patients with NAFLD.
OFP-02-011
Hexokinase domain-containing protein (HKDC1) is overexpressed in
and correlated with the histological progression of nonalcoholic fatty
liver disease
X. Ding
*
, X. Duan
*
Loyola University Medical Center, Pathology, Maywood, USA
Objective:
Nonalcoholic fatty liver disease (NAFLD) presents as either
steatosis or steatohepatitis. Steatohepatitis is progressive, but its patho-
genesis remains unclear. Hexokinase Domain Containing 1 (HKDC1) is a
recently identified hexokinase-like gene, which functions as a hexoki-
nase. Studies revealed that HKDC1 expression is associated with body
fat deposition; however, its association with NAFLD has never been
studied. The current study aims to explore HDCK1 expression in
NAFLD in the context of disease progression.
Method:
HKDC1 immunohistochemistry was performed on normal
livers (
n
= 22) and liver with NAFLD (
n
= 26, 11 cases with advanced
fibrosis). Immunostain intensity was graded as 0
–
1 (no or weak expres-
sion), 2 (moderate expression) and 3 (strong expression). Pearson
’
s Chi-
square test was used for statistical analysis.
Results:
Normal hepatocytes have minimal HKDC1 expression. HKDC1
expression is significant increased in NAFLD characterized by strong
expression in steatotic hepatocytes (
p
< 0.001). HKDC1 expression is
further accentuated in steatohepatitis with hepatocyte ballooning
(
p
=
p
< 0.001). Moreover, NAFLD with advanced fibrosis showed dif-
fuse strong HKDC1 expression.
Conclusion:
This is the first report showing increased HKDC1 expres-
sion in NAFLD. HKDC1 expression is positively correlated with the
histological progression of NAFLD. Hepatic fat accumulation might be
mediated by HKDC1; therefore, HKDC1 might be a potential target for
treatment of NAFLD.
OFP-02-012
Genetic profile of pancreatic neuroendocrine neoplasms G3
B. Konukiewitz
*
, M. Jesinghaus, A. M. Schlitter, A. Kasajima, K. Steiger,
G. Zamboni, W. Weichert, G. Klöppel, N. Pfarr
*
Technical University of Munich, Pathology, Germany
Objective:
Pancreatic neuroendocrine tumours (PanNETs) G1-G2 usual-
ly show an intact TP53 and RB1 status. In contrast, neuroendocrine car-
cinomas (PanNECs G3) are commonly TP53 and/or RB1 mutated. Little
is known about the genetic findings of NETs G3. In this study, we exam-
ined the genetic changes of NETs G3 and NECs G3 with the aim to define
the genetic profile of these two tumour families.
Method:
Tissue from 23 resected PanNENs, including 11 NETs G3 and
12 NECs, was examined by immunohistochemistry and next generation
sequencing applying a 409 gene panel.
Results:
NETs G3 harbored 49 mutations in 36 different genes, including
MEN1 alterations in 5/11 cases. DAXX and TP53 were mutated in 1/11
cases each, ATRX and RB1 showed no alterations. NECs harbored 63
mutations in 44 different genes, including 8/12 TP53 and 5/12 KRAS
mutations. Shared altered genes by NETs G3 and NECs were LRP1B
(3/23), ARID1A (2/23), CDKN2A (2/23), APC (3/23) and TP53 (9/23).
One NET G3 and two NECs did not show any mutations.
Conclusion:
PanNETs G3 and PanNECs differ substantially in their ge-
netic design. However, TP53 mutations may also occasionally occur in
PanNETs G3.
OFP-03-001
Reevaluation of clinical autopsies in the province of Vorarlberg/
Austria: A plea for diagnostic quality assessment in hospitals
N. Vitlarov
*
, D. Kocevska, J. Schneider, D. Susanne, F. Offner
*
Institute of Pathology, Feldkirch, Austria
Objective:
To detect discrepancies between clinical diagnoses and post-
mortem autopsy diagnoses through reevaluation of clinical and autopsy
records.
Method:
Clinical and autopsy records of 897 autopsies performed in
adults in 2005 (
n
= 325), 2010 (
n
= 293) and 2015 (
n
= 262) in
Vorarlberg, Austria were retrospectively reviewed. The discrepancies be-
tween clinical diagnoses and autopsy diagnoses were classified according
to Goldman criteria.
Results:
Autopsy rates were decreasing between 2005 and 2015 (2005:
19,6 %; 2010: 14,6 %; 2015: 10,2 %) and were paralleled by an increase
in major diagnostic errors (Goldman I + II). Therapeutically relevant
errors (Goldman I) increased from 12,5 % to 15,5 % to 16,7 %. There
was an increase of clinical underdiagnoses of neoplasms (2015: 2,5 %;
2010: 5,1 %; 2015: 9,9 %). Although the autopsy rate in cancer patients
was relatively stable (2005: 13,4 %; 2010: 11,1 %; 2015: 11,3 %), the
Monday, 4 September 2017, 08:30
–
12:00, G109
OFP-03 Joint Session: Autopsy Pathology / Cardiovascular
Pathology / Pathology in Favour of Developing Countries /
Electron Microscopy / Other Topics
Virchows Arch
(
2017
)
471
(
Suppl 1
):
S1
–
S352
S7