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

Abstracts
SO-072
Therapeutic and prognostic implications of an isolated Banff II
acute cellular rejection without tubulointerstitial component in
renal transplants
V . Broecker 1 , M . Hirzallah 2 , C .L . Bockmeyer 1 , P .A . Agustian 1 , M .E . Dämmrich 3 ,
A . Schwarz 4 , J .U . Becker 3
1 Hannover Medical School, Institute of Pathology, Hannover, 2 Klinikum
Region Hannover Krankenhaus, Oststadt-Heidehaus Medizinische Klinik
I, Hannover, 3 MHH, Institute of Pathology, Hannover, 4 Hannover Medical
School, Clinic for Nephrology and Hypertension, Hannover
Aims. In order to avoid unnecessary therapy it is debated intensely, whether
acute cellular rejection with Banff components v≥1, i0, t0 (v_only)
has the same therapeutic and prognostic implications as acute cellular
rejections with Banff components v≥1, i≥1, t≥1 (v_plus). We examined
this question retrospectively in renal transplant biopsies from a single
center.
Methods. All 23 renal transplant biopsies (from 23 patients) from our biopsy
archive with v_only were compared to 23 biopsies from 23 patients
with v_plus. All patients, v_only and v_plus, received therapy. They were
followed for 135 weeks ±106 (v_only) or 201 weeks ±151 (v_plus).
Results. No significant difference was found between v_only and v_plus
regarding donor sex, donor age, immunosuppressive regimen, recipient
age, time between transplantation and biopsy, number of glomeruli in
the biopsy, Banff components v, g, mm, ah, cg, cv, ci, ptc, ratio of of preglomerular
vessels with endothelialits to sum of preglomerular vessels,
C4d-positivity of preglomerular endothelium, of peritubular capillary
endothelium (Banff C4d), of glomerular endothelium, eGFR at biopsy,
kind of anti-rejection therapy, eGFR one week after initiation of anti-rejection
therapy, eGFR slope per week between biopsy and end of followup.
v_only had significantly more HLA-mismatches, a higher Banff ct
component and less cortical tubular interstitial edema.
Conclusions. The present data indicate marginal histological differences
between v_only and v_plus (with the exception of the defining Banff
components i and t). We could not find a difference regarding response
to anti-rejection therapy, transplant function or prognosis between
v_plus and v_only. The higher number of HLA-mismatches in v_only
might suggest that this rare lesion could be associated with donor specific
antibodies. We will examine this association further.
SO-073
Renal cell carcinoma and senescence: p400 as a novel prognostic
marker
S . Macher-Göppinger 1 , J . Lorenzo Bermejo2 , M . Hohenfellner3 , N . Wagener3 ,
P . Schirmacher1 , W . Roth1 1 2 University of Heidelberg, Institute of Pathology, Heidelberg, University of
Heidelberg, Institute of Medical Biometry and Informatics, Heidelberg, 3Uni versity Heidelberg, Department of Urology, Heidelberg
Aims. Mutations of the von Hippel-Lindau (VHL) tumor suppressor
gene cause hereditary and sporadic renal cell carcinomas (RCCs). The
best characterized function of VHL protein is suppression of the alpha
subunit of hypoxia inducible factor (HIF). Additional VHL functions
have been reported, including induction of senescence mediated by loss
of chromatin remodelling factor p400. Induction of senescence either by
oncogene activation or inactivation of tumor suppressors is considered
as a critical feature of mammalian cells to suppress tumorigenesis. Here,
we studied the expression of p400 in a large and well documented series
of RCCs with long term follow-up information.
Methods. Expression of p400 was examined by immunohistochemistry
using a tissue micro array containing RCC tumor tissue samples and
corresponding normal tissue samples from 932 patients. Regression
models were used to investigate the possible relationship between p400
expression and Ki-67 proliferative index, clinical and pathologic parameters
and disease-specific survival.
82 | Der Pathologe · Supplement 1 · 2012
Results. Loss of p400 expression was detected in 64% of all tumor specimens
and was associated with advanced tumor stage, higher grade
of malignancy and regional lymph node metastasis. Among well differentiated
RCCs, high proliferation (Ki-67 index 10+) was found in 10%
of carcinomas with a positive p400 expression, compared to 3% in p400
negative RCCs. Importantly, multivariate Cox regression indicated that
patients with high-proliferative tumors, those with p400-positive RCCs
have a 159% increased cancer-specific mortality risk compared to p400negative
RCCs.
Conclusions. Loss of p400 expression is common in RCCs and the proportion
of carcinomas with loss of p400 increases alongside advancing
tumor stage and decline of differentiation. In contrast, a subgroup of
tumors defined by high proliferation and expression of p400 shows significantly
shorter cancer-specific survival in multivariate analyses than
the subgroup of tumors with high Ki-67 labeling index without co-expression
of p400. Our data suggest that the highly proliferative, p400positive
subgroup of RCC represent tumors that are characterized by a
loss of the tumor-suppressive mechanism of senescence.
SO-074
Infiltration by tumor associated macrophages and CCR2/CCL7
expression correlates with brain metastases from clear cell renal
cell carcinoma
L .G . Wyler – von Ballmoos1 , C . Urrejola2 , P .H . Schraml1 , H . Moch1 1Institute of Surgical Pathology, University Hospital Zurich, Zürich, Switzerland,
2Institut of Pathology, University Hospital Basel, Basel, Switzerland
Aims. Renal cancer patients with brain metastasis have a poor prognosis.
The mechanisms, by which renal cancer metastasize to the brain is not
entirely understood. The Goal of this study was to find out more about
pathways of metastases from clear cell renal cell carcinoma (ccRCC) and
whether the expression of CCL2, CCL7, CCR2 and CXCR4 by tumor
cells and tumor associated macrophages (TAMs) correlates with brain
metastasis and/or outcome.
Methods. Among 40’021 routine autopsies, the reports from those 636
with metastatic renal cancer were rewied and the metastatic sites were
analyzed. For imunohistochemical staining tissue microarrays were
constructed from biopsy samples of 333 primary RCCs and 51 brain metastases
from ccRCCs. Stainings for CCL2, CCL7, CCR2, CXCR4 and
CD68 were analyzed and compared.
Results. Hematogenous metastases were present in 39% of the autopsy
cases, with most frequent involvement being lung (75%), liver and bone
(40% each), and soft tissue (34%). Brain metastases were observed in 15%.
The rate of brain metastases was higher in patients with lung metastases,
but was also observed in patients without thoracic metastases and
as isolated brain metastases. A strong expression of CXCR4 was seen in
31% of primary ccRCCs and 45% of brain metastases however a moderate
expression was seen in over 80% in both. CCR2 and CCL7 showed a
significantly higher expression in brain metastases of ccRCCs compared
to primary ccRCCs (p40) macrophage infiltrate. Within these CCR2 expressing TAMs correlated
with higher Fuhrman grade (p=0.003) and were more frequent in
brain metastases (p