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

Abstracts
the nasopharyngeal tonsil might relate to the anatomical restriction of
respiratory surface epithelium to this type of tonsil and might thereby
give a clue of the primary site of malignant transformation by EBV.
DO-090
Analysis of human papilloma virus (HPV) and Epstein-Barr virus
(EBV) in salivary gland adenocarcinomas
E . Senft1 , H . Kreipe1 , K . Hussein1 1Hannover Medical School, Institute of Pathology, Hannover
Aims. Viruses are known to be associated with neoplastic proliferation,
e.g. epitheliotropic human papilloma virus (HPV) can be detected in
squamous neoplasms such as cervix carcinoma and oropharynx carcinoma
while Epstein-Barr virus (EBV) infects B cells and can induce malignant
lymphomas. Furthermore, EBV persists in the ductal epithelial
cells of salivary glands and can be associated with solid neoplasms such
as benign Warthin tumour. Systematic analyses have been performed
in squamous carcinomas of the head and neck but not in salivary gland
adenocarcinomas.
Methods. Histological re-evaluation and selection of samples: adenoidcyctic
carcinomas (n=20), adenocarcinomas, NOS (n=17), mucoepidermoid
carcinomas (n=11), pleomorphic adenoma (n=4), carcinoma
ex pleomorphic adenoma (n=3), non-neoplastic salivary glands (n=65).
Analysis of multi-blocks with a total of 120 formalin-fixed and paraffinembedded
(FFPE) tissue samples by HPV immunhistochemistry and
EBER in situ hybridisation. DNA extraction from FFPE tumour samples
and evaluation of HPV by multiplex PCR.
Results. HPV and EBV were not detectable in salivary gland carcinomas.
Conclusions. This is the first systematic analysis which demonstrates that
the two human pathogenic viruses HPV and EBV are not involved in the
pathobiology of salivary gland adenocarcinomas.
DO-091
SOX2 amplification is a common event in sinunasal squamous cell
and undifferentiated carcinomas
F . Göke1 , A . Franzen2 , R . Menon2 , S . Huss3 , D . Boehm2 , W . Vogel2 , F . Bootz4 ,
S . Ihrler5 , A . Schroeck4 , S . Perner1 1 2 3 University Hospital Bonn, Pathology, University Hospital Bonn, University
Hospital Cologne, Institute of Pathology, 4University Hospital Bonn,
Head and neck department, 5Laboratory for Dermatohistology and Oral
Pathology
Aims. Although carcinomas of the nasal cavities are known to differ significantly
from other cancers of the head and neck, regarding causing
noxa, clinical behavior, and treatment, they share histological appearance.
SOX2, a transcription factor-coding gene located at 3q26.33, is known
to be recurrently amplified in squamous cell carcinomas (SCCs) of the
lung, esophagus, skin, penis, cervix uteri and oral cavity. The aim of our
study was to assess if SOX2 amplifications also occur in different tumor
entities of the paranasal sinuses.
Methods. Using fluorescence in-situ hybridization, we assessed for SOX2
amplification status in a cohort consisting of sinonasal SCCs (n=65), sinonasal
undifferentiated carcinomas (SNUC, n=18), adenocarcinomas
(n=25), and adenoid cystic carcinomas (n=18). Furthermore, we performed
SOX2 immunohistochemical staining to quantify protein expression.
Results. We detected SOX2 amplifications in 36% of sinunasal SCCs, 35%
of SNUCs, 9% of adenocarcinomas, but none of the adenoid cystic carcinomas.
Moreover, we found that the SOX2 amplification is associated
with a SOX2 protein overexpression in SCCs and SNUCs.
Conclusions. SOX2 amplification is not an organ site specific event, but
is a frequent genetic alteration occurring in SCCs of various organs. Since
SNUCs also harbor SOX2 amplifications in similar frequencies, we
36 | Der Pathologe · Supplement 1 · 2012
hypothesize that SNUCs may be undifferentiated SCCs of the sinunasal
cavity.
DO-092
Expression of differentiation factor caspase 14 in oral squamous
carcinomas
C . Scharenberg1 , H . Kreipe1 , K . Hussein1 1Hannover Medical School, Institute of Pathology, Hannover
Aims. Caspase 14 is not involved in apoptosis (in contrast to all other
caspase family members) but in differentiation of squamous epithelia.
Caspase 14 is expressed mainly in the suprabasal layers, particularly the
Str. intermedium/spinosum. Systematic analyses have been performed
in cervix carcinomas and skin cancer but not oral cavity squamous carcinomas.
Methods. Histological re-evaluation and selection of samples: squamous
carcinomas of the oral cavity (n=30) and oral leukoplakia (n=10). Caspase
14 expression analysis by immunhistochemical evaluation of formalin
fixed and paraffin embedded (FFPE) tissue samples.
Results. Nuclear and cytoplasmatic caspase 14 expression is evident in
non-neoplastic epithelial cells of the Str. intermedium but absent or weak
in the basal and superficial layers. In leukoplakia the protein expression
is increased in cells with keratinisation. In invasive lesions, caspase 14 is
mainly expressed in the cells with keratinisation but absent or weak in
neoplastic cells without keratinisation.
Conclusions. This is the first experimental evidence that differentiation
factor caspase 14 is expressed in oral cavity squamous carcinomas.
Similar to leukoplakia expression of caspase 14 is increased in carcinoma
cells with keratinisation.
DO-093
FGFR1 amplification in metastatic squamous cell carcinoma of the
head and neck – a potential target for a rational therapy?
F . Göke1 , A . Franzen2 , R . Menon2 , R . Kirsten2 , D . Boehm2 , W . Vogel2 , F . Bootz3 ,
A . Schroeck3 , S . Perner1 1 2 3 University Hospital Bonn, Pathology, University Hospital Bonn, University
Hospital Bonn, Head and neck department
Aims. Currently, patients with FGFR1 amplified squamous cell lung cancers
(L-SCC) are treated in phase I clinical trials using small molecule
inhibitors. Of interest, SCC of the lung share common molecular alterations
with squamous cell head and neck cancers (HN-SCC). Aim of our
study is to assess if HN-SCCs also harbor FGFR1 amplifications. Furthermore,
we aim to identify a HN-SCC cell line harbouring FGFR1 amplification
and inhibit cell proliferation using a small molecule inhibitor.
Methods. We put together a cohort of 227 patients suffering from HN-
SCC, with 97 of these suffering from metastatic disease. Primary tumors
and, where available, metastatic tumors were assessed for FGFR1 copy
number status using fluorescence in-situ hybridization (FISH). We tested
different cell lines for FGFR1 amplification status and inhibited these
with small molecule inhibitors.
Results. 20.3% of primary HN-SCC displayed FGFR1 amplifications. Of
interest, almost all metastatic tumor samples revealed a FGFR1 amplification
if the corresponding primary tumor harbored the amplification.
The cell lines HN and SCC-25 harboured FGFR1 amplifications. HN cell
proliferation was inhibitable with small molecule inhibitors.
Conclusions. FGFR1 amplification frequently occurs in primary and metastatic
HN-SCC and proves as a potential target for small molecule therapy
in non-operable or metastatic disease. Furthermore, cell growth of
FGFR1 amplified cell lines is inhibitable with small molecule inhibitors.
Additional functional studies and subsequent clinical trials are needed
for further validation of our findings.