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

Abstracts
SA-P-008
Correlation of anti-PHH3 positive mitoses to pathological response
in neoadjuvantly treated breast cancer
S . Timme 1 , M . Becker 2 , E . Stickeler 2 , P . Bronsert 1 , L . Reischuck 2 , L . Bogatyreva 3 ,
D . Hauschke 3 , A . zur Hausen 4 , M . Werner 1
1 Institute of Pathology, University Medical Center, Freiburg, 2 Department of
Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg,
3 Institute of Medical Biometry and Medical Informatics, University Medical
Center, Freiburg, 4 Department of Pathology, GROW, School for Oncology
and Developmental Biology, Maastricht University Medical Center, Maastricht,
Netherlands
Aims. We evaluated breast cancer (BC) core biopsies taken before neoadjuvant
chemotherapy (NACT) by immunohistochemistry using anti-PhosphohistoneH3
antibody (PHH3) to determine the mitotic count.
The data were correlated to clinicopathological parameters including
intrinsic subtypes as well as the histopathological regression of resected
tumour specimens after NACT with Epirubicin/Cyclophosphamide
(EC) and Taxotere.
Methods. 72 patients with either triple negative (21/72) or luminal type
(51/72) BC obtained NACT with EC and Taxotere. Thereafter, tumour
regression was analyzed in resection specimens using a semiquantitative
score from 0 (no effect) to 4 (no cancer cells) according to Sinn et al.
(1994). Pathological complete response (pCR) was defined as no residual
invasive carcinoma (score 3+4). In 16/72 cases (22.2%) pCR occurred; 9/16
(56.25%) were TNBC and 7/16 were luminal type BC (ER and/or PrR+/
HER2−). In the pre-treatment biopsies immunohistochemical stainings
with PHH3 were performed and mitotic figures were evaluated in 10 high
power fields (HPF). The number of mitoses detected by PHH3 was correlated
to different clinicopathological parameters determined before treatment
(intrinsic subtype, WHO-type, grading, tumour size and nodal
stage) and to regressive changes/pCR after therapy by univariate statistical
analyzes (using SPSS v 18).
Results. The number of PHH3-detected mitoses correlated significantly
with the tumour grading (p=0.001), but there was no correlation with
WHO-type, tumour size or nodal stage. PHH3/10 HPF differs significantly
between the two intrinsic subtypes (p=0.003). PHH3 expression
alone was no predictor for pCR (p=0.399). But tumours with 11 or
more mitoses/10 HPF achieved significantly more often pCR than those
with under 11 mitoses/10 HPF (p=0.031). Furthermore, luminal type
BC with 11 or more mitoses/10 HPF and also TNBC had significantly
more frequent pCR than luminal type BC with under 11 mitoses/10 HPF
(p=0.016).
Conclusions. Strong proliferating BC (11 or more mitoses/10 HPF) have
significantly more pCR compared to low proliferating tumours (under
11 mitoses/10 HPF) after NACT with EC and Taxotere. Furthermore,
mitoses detected by PHH3 are a discriminator for luminal type BC to
predict pCR, because luminal type BC under 11 mitoses/10 HPF rarely
reach pCR. Thus, the determination of mitoses by PHH3 may be recommended
especially for luminal type BC before NACT with EC and
Taxotere.
SA-P-009
Transitions between flat epithelial atypia and low-grade ductal
carcinoma in situ of the breast
S . Aulmann1 , F . Mietzsch1 , R . Penzel1 , P . Schirmacher1 , H .P . Sinn1 1University of Heidelberg, Institute of Pathology, Heidelberg
Aims. Flat epithelial atypia (FEA) of the breast typically is a localised alteration
involving only few, neighbouring terminal ducto-lobular units
(TDLUs). However, occasionally there are cases with extensive FEA and
morphological evidence of direct transitions between FEA and classical
ductal carcinoma in situ (DCIS).
Methods. To investigate the relationship of FEA and DCIS in these cases,
we microdissected multiple foci of the respective lesions in a series
142 | Der Pathologe · Supplement 1 · 2012
of 10 cases and performed comparative allelotyping using a panel of 14
LOH markers. In addition, phylogenetic tree models were calculated on
the basis of mitochondrial DNA sequencing to visualise the clonal relationship
of the different lesions.
Results. FEA and lg-DCIS shared the majority of chromosomal imbalances,
loss of diverging alleles was not detected in any of the 10 cases.
mtDNA sequencing and phylogenetic tree clustering revealed direct
transitions between FEA and lg-DCIS in all 10 cases. However, in three
patients, additional foci of FEA were present which were not directly related
to the rest of the FEA and the lg-DCIS.
Conclusions. In conclusion, our data demonstrate the presence of direct
transitions between FEA and lg-DCIS and support the interpretation of
foci of FEA as part of the lg-DCIS in those unusual cases in which multiple
areas of FEA are interspersed with areas of classical lg-DCIS and
direct transitions of both lesions are apparent.
SA-P-010
Different cytoplasmic and nuclear PARP expression patterns in
hereditary and non-hereditary breast cancer
M .-L . Klauke1 , N . Hoogerbrugge1 , J . Budczies2 , P . Bult1 , J .H .J . van Krieken1 ,
C . Denkert2 , B .M . Müller2 1Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands,
2Charité Hospital, Institute of Pathology, Berlin
Aims. High cytoplasmic poly (adenosine diphosphate-ribose) polymerase
(PARP) expression in non-hereditary breast cancer correlates with an
aggressive tumor pattern and a poor long-term prognosis. Our study was
designed to compare cytoplasmic and nuclear PARP expression between
hereditary and non-hereditary breast cancer.
Methods. Tissue micro arrays containing 39 familiar and 39 non-hereditary
formalin-fixed, paraffin embedded breast cancer tumor samples
were immunohistochemically analyzed for cytoplasmic (cPARP) and
nuclear (nPARP) PARP expression. Stained slides were digitized and
evaluated using the VM Slide Explorer. The intensity and percentage
of positive tumor cells were used to calculate an immunoreactive score
(IRS), which was divided into three subgroups defined as low (IRS 0–2),
intermediate (IRS 3–4) and high (IRS 6–12) expression. The mean age at
diagnosis in patients with familiar breast cancer was about 45±11 years
and in patients with non-hereditary breast cancer about 65±12.1 years.
Results. cPARP and nPARP expression patterns were significantly different
in hereditary and non-hereditary breast cancer. cPARP expression
in hereditary breast cancer was low in 33.3%, intermediate in 25.6% and
high in 41.0% of cases. In contrast, cPARP in non-hereditary breast cancer
was low in 59.0%, intermediate in 25.6% and high in 15.4% of cases.
Statistical analysis showed that cPARP expression was significantly higher
in hereditary compared to non-hereditary breast cancer (p=0.008,
χ2-test for trends). Hereditary breast cancer showed a significant lower
intermediate nPARP expression (23.1%) than non-hereditary breast cancer
(59.0%; p=0.005, χ2-test).
Conclusions. PARP expression in hereditary and non-hereditary breast
cancer differs significantly, which might be related to the higher frequency
of BRCA1 or 2 mutations in hereditary breast cancer and is compatible
with a role of PARP-1 in DNA repair and genomic stability. Because patients
with hereditary breast cancer have a poor long-term prognosis and
show very often an aggressive tumor pattern the overall higher cPARP
expression found in this subgroup suggests that high cPARP expression
might be correlated with an aggressive tumor pattern and a poor longterm
prognosis.