96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

FR-P-129
Alpha-1-antitrypsin-PiZ-antibody ATZ11 recognizes von Willebrand
factor (vWF): diagnostic and pathogenetic aspects
K . Hiththetiya 1 , H . Zhou 1 , S . Steiner 1 , H .J . Hertfelder 2 , H .-P . Fischer 1
1 University Hospital Bonn, Institute of Pathology, Bonn, 2 University Hospital
Bonn, Institute of Experimental Hematology and Transfusion Medicine,
Bonn
Aims. Antibody ATZ11 which is directed specifically against the mutated
Alpha-1-antitrypsin PiZ will be tested on further specific binding
sites independent of PiZ. The identity of the underlying ATZ11-binding
proteins will be analysed. Diagnostic und pathogenetic relevance of this
specific cross-reaction will be discussed.
Methods. Comparative immunhistochemical analysis, imunoelectronmicroscopic
analysis, Western-blots of cultivated human vitelin cord
endothelial cells and thrombocyte aggregates.
Results. ATZ11-specific epitope is found immunohistochemically on
megakaryocytes, platelets, endothelial cells of arteries, veins and some
capillaries of normal human tissues. More extensive staining is found
in portal vessels of end-stage liver cirrhoses. Neoexpression is found in
sinusoidal endothelial cells of actively fibrosing liver diseases, especially
in strongly progressive alcoholic steatohepatitis. Microvascular bed of
hepatocellular carcinomas and hepatocellular adenomas remains unstained.
The staining reactivity corresponds to that of von Willebrand
factor (VWF) and P-Selectin. It is independent from the presence of hepatocellular
AAT deposits of PiZ type and AAT genotype. The epitope
can be detected in Weibel-Palade bodies (WPB) of human vitellin cord
endothelial cells (HUVEC) and in the cytoplasm of patelets by immunoelectronmicroscopy.
ATZ11-Western blotting of HUVEC and patelets
visualizes a 240 kD molecule which is in the spectrum of the molecular
weights of multimeric VWF. VWF deficient serum samples lack this
ATZ11-binding molecule.
Conclusions. Apparently ATZ11 binds to a conformation-dependent epitope
of VWF which might reflect a special functional state of this protein.
ATZ11 expression in sinusoids of actively fibrosing steatohepatitis
highlights the possible role of VWF in sinusoidal occlusion by locally
activated coagulation.
Poster: Pneumopathologie
FR-P-130
MAdL- a new specific marker for adenocarcinomas of the lung
H . Schultz1 , S . Marwitz1 , B . Baron-Lühr1 , G . Zissel2 , C . Kugler3 , K .-F . Rabe3 ,
P . Zabel1 , E . Vollmer 1 , J . Gerdes1 , T . Goldmann1 1 2 Research Center Borstel, Borstel, University of Freiburg, Department for
Pneumology, Freiburg, 3Hospital Großhansdorf, Großhansdorf
Aims. Although the common immunohistochemical markers are well
suitable for sub-differentiation a fraction of indistinct cases of NSCLC
still remains, demanding upgrades of the panel by new markers.
Methods. Here we report the generation and evaluation of a new monoclonal
antibody denoted by “Marker of adenocarcinomas of the lung”
(MAdL), which was raised against the cytoplasmatic fraction of primary
isolated human alveolar epithelial cells type II.
Results. Upon screening, one clone was identified as a marker for alveolar
epithelial cells type II, alveolar macrophages and particularly adenocarcinomas
of the lung. With an optimized staining procedure for formalin
fixed tissues this antibody was evaluated together with the established
markers TTF-1, SP-A, pro SP-B and Napsin A in a large-scale study on
a series of 362 lung cancer specimens. MAdL displays a high specificity
for adenocarcinomas of the lung together with a sensitivity of 76.5% and
is able to provide independent additional diagnostic information to the
established markers.
Conclusions. We conclude that MAdL is a new lung specific marker for
adenocarcinomas, which expands sub-differentiation in a notable portion
of non-small cell lung cancers.
FR-P-131
Pulmonary haptoglobin (pHp) can be used as a new specific marker
for adenocarcinomas of the lung
M . Abdullah1 , S . Marwitz1 , D . Kähler1 , H . Schultz1 , C . Kugler2 , P . Zabel3 ,
E . Vollmer 1 , T . Goldmann1 1 2 Research Center Borstel, Clin . & Exp . Pathology, Borstel, Hospital Großhansdorf,
3Research Center Borstel, Borstel
Aims. There are novel chemo-therapeutic approaches which recently have
been developed for NSCLC, known as a largely chemo-resistant tumour.
Substantial differences have been shown between adenocarcinomas and
squamous cell carcinomas with regard to the adequate therapeutic regimens.
Therefore, sub-differentiation of NSCLC is currently getting more
into focus and increasingly turning out to be a central element within
therapeutic decisions. In this study we analyzed the expression of pulmonary
haptoglobin (pHp) in human lung cancer tissues and compare it
to common markers of adenocarcinomas.
Methods. Immunohistochemistry and heat-induced antigen-retrieval
were conducted. For detection, a one-step polymer-system was applied.
119 formalin-fixed, paraffin-embedded tumour tissues were immunohistochemically
analyzed for expression of php, TTF-1, SP-A, SP-B and
Napsin.
Results. Pulmonary haptoglobin was expressed in 35 of 72 (48.6%) adenocarcinomas
of the lung, [TTF-1 (79.1%), SP-A (51.3%), SP-B (48.6%) and
Napsin (84.1%)]. Expression of pHp in squamous cell carcinomas (N=47)
was absent. A proportion of cases exclusively express either pHp and
Napsin (pHp+/Napsin+: 4.7%) or pHp and TTF-1 (pHp+/TTF-1+: 3.1%).
7.8–14% of the samples would have caused difficulties if the expression of
pHp would not have been addressed.
Conclusions. SP-A and SP-B are specific markers for adenocarcinomas
with a limited sensitivity compared to TTF1; the same holds true for
pHp. Therefore, the inclusion of pHp as an additional marker in the panel
has serious impact on diagnostics and therapy.
FR-P-132
The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression
in human non-small cell lung cancer
Y . Chen1 , T . Cui1 , L . Yang 1 , M . Mireskandari1 , T . Knösel1 , Q . Zhang1 , M . Pacyna-
Gengelbach2 , I . Petersen 1
1 2 University Hospital Jena, Jena, University Hospital Charité, Berlin
Aims. The constitution and expression patterns of cytokeratin filaments
in human epithelial neoplasms are complex and distinctive. The aims
of this study were analysis of the expression of cytokeratins and evaluation
of their diagnostic application in human non-small cell lung cancer
(NSCLC).
Methods. mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19
was analyzed by Northern blotting. Protein expression of CK5/6, CK7,
CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue
microarrays.
Results. Northern blotting showed that CKs were highly expressed in
human bronchial epithelial cells and/or small airway epithelial cells.
In NSCLC cell lines, the expression pattern of CKs was heterogeneous.
In the survey of protein expression of CKs in 95 primary lung tumors,
we found that CK5/6, CK14, and CK17 proteins were highly expressed
in squamous cell carcinoma compared to adenocarcinoma (p=0.001,
p=0.030, and p=0.001, respectively) and higher expression is significantly
linked to lower grading (p=0.006, p=0.002, and p=0.001, respectively),
while increased expression of CK7 and CK18 was observed in adenocarcinoma
(p=0.001, respectively).
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