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

Abstracts
was calculated from the date of diagnosis until death or loss to follow-up
evaluation. Univariate survival analysis was computed by means of the
Kaplan-Meier method and significance levels were assessed by means of
the log-rank test.
Results. The percentage of MCM6 expressing tumor cells ranged from
27.6% to 97.0%, with a mean of 82.8%. A high MCM6 expression level
of more than 80% positive cells was associated with a significantly longer
overall survival time (130.5 months) compared to patients with a low
MCM6 expression level of less than 80% (58.7 months, p=0.0016).
Conclusions. Immunohistochemical detection of MCM6 seems to be a
promising marker for predicting the outcome in patients with colorectal
cancer.
FR-P-089
Lymphangiogenesis in regional lymph nodes is an independent
prognostic marker in rectal cancer patients after neoadjuvant
treatment
M . Muders1 , C . Jakob1 , D . Aust1 , G . Folprecht2 , K . Datta3 , G .B . Baretton1 1University Hospital Carl Gustav Carus at the University of Dresden, Institute
of Pathology, Dresden, 2University Hospital Carl Gustav Carus at the University
of Dresden, Department of Internal Medicine, Dresden, 3University of
Nebraska Medical Center, Omaha, NE, United States
Aims. One of the major prognostic factors in rectal cancer is lymph node
metastasis. The formation of lymph node metastases is dependent on
the existence of a premetastatic niche. An important factor preceding
metastasis are lymph vessels which are located in the lymph node. Accordingly,
the occurrence of intranodal lymphangiogenesis is thought to
indicate distant metastasis and worse prognosis. In this study we evaluate
the significance of lymph node lymphangiogenesis in a cohort of rectal
cancer patients who are treated with neoadjuvant radiochemotherapy.
Methods. We studied formalin fixed, paraffin embedded adenocarcinomas
and regional lymph nodes of 203 rectal cancer patients who were
treated with neoadjuvant radiochemotherapy and consecutive curative
surgery with cancer free surgical margins (R0). Regional lymph nodes
were detected by immunohistochemistry for podoplanin (D2-40). These
results were then correlated with disease free survival and stage of disease
using standard statistical methods.
Results. The presence of lymphatic vessels in regional lymph nodes significantly
affects the disease-free survival in univariate and multivariate
analyses. In contrast, there was no correlation between peritumoral or
intratumoral lymph vessel density and prognosis.
Conclusions. Our study demonstrates the importance of lymphangiogenesis
in regional lymph nodes after neoadjuvant radiochemotherapy
and consecutive surgery as an independent prognostic marker. Staining
for intranodal lymphangiogenesis and methods of intravital imaging of
lymphangiogenesis and lymphatic flow may be a useful strategy to predict
long-term outcome in rectal cancer patients. Furthermore, addition
of VEGF-blocking agents to standardized neoadjuvant treatment schemes
might be indicated in advanced rectal cancer.
FR-P-090
FGFR1 amplification in primary and lymph node metastatic
colorectal cancer
A . Göke1 , F . Goeke1 , D . Boehm1 , R . Menon1 , W . Weichert2 , R . Buettner3 ,
S . Perner1 1Universitätsklinikum Bonn/Institut für Pathologie, Institute of Prostate
Cancer Research, 2University Hospital of Heidelberg/Institute of Pathology,
3University Hospital of cologne/Institute of Pathology
Aims. Previous studies showed that up to 20% of squamous cell lung cancers
display an amplification of the fibroblast growth factor receptor 1
(FGFR1) gene and that these cases are potentially sensitive to treatment
112 | Der Pathologe · Supplement 1 · 2012
with a specific inhibitor. By exploring the largest publicly available database
of somatic copy number changes in tumors (www.broadinstitute/tumorscape.org),
we found evidence that also a subset of colorectal
cancers (CRC) might be characterized by FGFR1 amplification. Consequently,
we evaluated the frequency of FGFR1 amplifications in both
primary and lymph node metastatic CRC by applying in-situ detection.
Moreover, our objective was to determine whether FGFR1 can be used
as a potential therapeutic drug target in primary and progressed CRC.
Methods. We assessed 450 paraffin embedded primary CRC samples embedded
in a tissue microarray format. Of these, 94 cases had corresponding
lymph node metastases. A target probe located on the FGFR1 locus
spanning 8p11.23 to 8p11.22 and a centromeric reference probe were used
to determine the FGFR1 amplification status using fluorescence in situ
hybridization (FISH). Furthermore, CRC cell lines are currently being
tested for their FGFR1 amplification status. FGFR1 amplified cell lines
will then be treated with a FGFR specific inhibitor.
Results. 4.2% (19/450) of primary CRC displayed FGFR1 amplification. Of
primary CRCs with corresponding lymph node metastasis 4.2% (4/94)
harbored FGFR1 amplification in both, and 2.1% (2/94) cases showed
FGFR1 amplification in only the primary tumor, but not in the metastasis.
Conclusions. FGFR1 amplification is a recurrent event found in CRC.
Furthermore, we suggest that FGFR1 amplification is a clonal event in
tumor progression since the FGFR1 amplification status transferred to
the corresponding lymph nodes in most of our cases. Our study may indicate
novel therapeutic possibilities for patients suffering from primary
and metastatic CRC.
FR-P-091
Neoadjuvant treated liver metastasis of colorectal cancer:
Is the histopathological regression grade a useful predictor for
survival?
P . Bronsert1 , S . Ruhm2 , H . Neef3 , S . Timme1 , M . Werner1 , G . Illerhaus2 ,
F . Makowiec3 1Albert-Ludwigs-University Freiburg, Institute of Pathology, Freiburg,
2Albert-Ludwigs-University Freiburg, Department of Haemato-Oncology,
Freiburg, 3Albert-Ludwigs-University Freiburg, Department of General and
Visceral Surgery, Freiburg
Aims. Surgical treatment of resectable liver metastasis of colorectal cancer
(CRC-LM) after neoadjuvant therapy (NACT) is a common method
worldwide. For several tumour entities (e.g. esophageal, gastric and
breast cancer) histopathological tumor regression grade (TRG) is well
known as a significant predictive marker. In terms of CRC-LM less is
known about the predictive potential of TRG in relation to overall survival
(OS). In this study we determined the TRG of neoadjuvant treated
CRC-LM and correlated those data with OS and other clinicopathological
parameters.
Methods. The collective contains 89 patients, 68 (76%) of which were
treated with an Oxaliplatin or Irinotecan containing NACT and 21 (27%)
of which were treated with a “targeted therapy” using antibodies. Median
NACT period time was 6 month (1–24 months) and the average
number of liver metastasis per patient was 2 (1–11 metastasis). Complete
hepatical resection (R0) was observed in 80 patients (89%), a complete
overall resection (R0, cm0) in 69 patients (77%). From formalin fixed paraffin
embedded tumor tissue of the resection specimen haematoxylin
and eosin staining was performed. We determined the TRG according
to a previously published score from Rubbia-Brandt et al. – a quantitative
scoring system ranging from score 1 (complete regression) to score 5 (no
cytopathic effect). After scoring, the regression was correlated to clinicopathological
parameters including patient survival.
Results. Most patients (62/89; 69%) showed a poor TRG (score 4/5) and
24/89 (27%) showed a moderate response (score 2/3). A mere 3/89 patients
(4%) had a complete regression (score 1). The 5-year survival rate of all
89 patients was 41%. OS of patients with complete regression was 100%;