96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
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DO-094<br />
Do activated fibroblasts influence epi<strong>der</strong>mal growth factor receptor<br />
(EGFR) inhibitor sensitivity in oral squamous cell carcinoma<br />
cells (OSCC)?<br />
P . Richter 1 , N . Neumann 2 , J . Schulte 3 , K . Schult 1 , S . Weisheit 4 , M . Franz 5 ,<br />
O . Guntinas-Lichius 6 , C . Liebmann 4 , I . Petersen 1 , A . Berndt 1<br />
1 Jena University Hospital, Institute of Pathology, Jena, 2 University Hospital<br />
Zurich, Institute of Surgical Pathology, Zurich, Switzerland, 3 Ludwig-Maximilian-University,<br />
Munich, Großha<strong>der</strong>n Medical Center/Department of Cardiac<br />
Surgery, München, 4 Friedrich Schiller University Jena, Institute of Biochemistry<br />
and Biophysics, Jena, 5 Jena University Hospital, Clinic for Internal<br />
Medicine I, Jena, 6 Jena University Hospital, Department of Otorhinolaryngology,<br />
Jena<br />
Aims. Although EGFR is involved in development of OSCC and EGFRinhibitor<br />
sensitivity could be shown in OSCC cell lines, a therapeutic<br />
benefit of an EGFR-inhibitor therapy can be observed only in a minority<br />
of patients. It was suggested that the carcinoma microenvironment have<br />
modulating effects on inhibitor sensitivity in vivo. One possible hypothesis<br />
is that carcinoma associated fibroblasts induce phenotype changes<br />
such as epithelial-mesenchymal transition (EMT) which are accompanied<br />
by alterations in EGFR signalling. Thus, the study was aimed at investigating<br />
the influence of growth factor activated fibroblasts on EGFRinhibitor<br />
sensitivity of OSCC in vitro applying Gefitinib.<br />
Methods. “Activated” fibroblasts were generated by stimulation of<br />
hTERT-BJ1 fibroblasts with TGFbeta1, PDGFAB, aFGF, and TGFbeta1/<br />
aFGF, respectively. They were characterized with regard to proliferation,<br />
expression of fibroblast markers, activation of EGFR signalling, and<br />
the capability to induce OSCC cell invasion as well as their Gefitinib<br />
sensitivity using immunohistochemistry, western blotting, rtRT-PCR,<br />
MTT test and Boyden chamber assay. Furthermore, Gefitinib sensitivity<br />
was evaluated in different OSCC cell lines by MTT test. The impact of<br />
TGFbeta1 and TGFbeta1/aFGF activated fibroblasts on EGFR inhibitor<br />
sensitivity was assessed by pre-culturing of OSCC cells in fibroblast conditioned<br />
media.<br />
Results. In vitro activated fibroblasts showed a strong upregulation of<br />
ASMA and fibronectin due to stimulation with TGFbeta1. PDGFAB stimulation<br />
induced proliferation with up-regulation of EGFR and pAKT.<br />
aFGF and TGFbeta/aFGF stimulation resulted in an intermediate phenotype.<br />
TGFbeta1 stimulated fibroblasts exhibited the highest capability<br />
to induce invasion in the OSCC cell line PE/CA-PJ15 with upregulation of<br />
N-cadherin. Interestingly, activated fibroblasts differed in their Gefitinib<br />
sensitivity (TGFbeta-stim.=”low” and PDGFAB stim.=”high”). OSCC<br />
cell lines tested so far show a different Gefitinib sensitivity. Furthermore,<br />
pre-culturing in fibroblast conditioned medium leads to a partial reversibility<br />
of the Gefitinib effect.<br />
Conclusions. Results indicate that: 1) EGFR inhibition by Gefitinib<br />
affects OSCC cells as well as activated stromal fibroblasts, 2) the different<br />
Gefitinib sensitivity of fibroblast phenotypes may lead to a selective<br />
accumulation of myofibroblasts during treatment, and 3) OSCC cell sensitivity<br />
is modulated by stromal fibroblasts.<br />
DO-095<br />
Evaluation of post-transplant lymphoproliferative diseases<br />
(PTLD) with manifestation in the oral cavity<br />
C . Tiede1 , B . Maecker-Kolhoff 2 , H . Kreipe1 , K . Hussein1 1 2 Hannover Medical School, Institute of Pathology, Hannover, Hannover<br />
Medical School, Hannover<br />
Aims. Inspection of the oral cavity can be easily performed in transplanted<br />
patients with an oral tumour mass and suspected Epstein-Barr virus<br />
(EBV)-associated post-transplant lymphoproliferative disease (PTLD).<br />
We aimed to evaluate the main sites of manifestation and the morphological<br />
subtypes of PTLD in the oral cavity.<br />
Methods. Evaluation of histomorphology and clinical data on early lesion,<br />
polymorphic, and monomorphic PTLD. Total cohort of 212 patients<br />
(median age 9 years, range 0.5–70 years, 57% males/43%females, 75.5%<br />
children/24.5% adults).<br />
Results. Oral cavity PTLD manifestation was found in 61/212 patients<br />
(29%): 42/61 early lesion PTLD (20%), 12/61 polymorphic PTLD (6%)<br />
and 7/61 monomorphic PTLD (3%). Tonsils were the most frequent site<br />
of manifestation (n=57/61, 93%) including early lesion PTLD (n=42/57,<br />
74%), polymorphic PTLD (n=12/57, 21%) and monomorphic B cell PTLD<br />
(n=3/57, 5%). Other localisations were gingiva (n=2/61, 3%; EBV+ plasmocytomas),<br />
maxillary bone (n=1/61, 1.5%; EBV+ plasmocytomas) and<br />
larynx (n=1/61, 1.5%; EBV-T-cell PTLD).<br />
Conclusions. Tonsils are the main site of PTLD manifestation in the oral<br />
cavity and comprise mainly benign early lesion PTLD and polymorphic<br />
PTLD. Oral cavity monomorphic PTLD is rare and is located outside of<br />
the tonsils in a consi<strong>der</strong>able proportion (n=4/7, 57%) of cases.<br />
DO-096<br />
Non-sebaceous lymphadenoma of salivary glands: proposed<br />
development from intraparotid lymph nodes and risk of misdiagnosis<br />
C . Weiler1 , A . Agaimy2 , P . Zengel3 , J . Zenk4 , T . Kirchner1 , S . Ihrler5 1 2 Ludwig Maximilian University, Institute of Pathology, München, University<br />
Hospital Erlangen, Institute of Pathology, Erlangen, 3Ludwig Maximilian<br />
University, Head and Neck Surgery, München, 4University Hospital Erlangen,<br />
Head and Neck Surgery, 5Laboratory for Dermatohistology and Oral Pathology,<br />
München<br />
Aims. Non-sebaceous lymphadenoma (NSLA) is a rare benign salivary<br />
gland tumour composed of lymphoid and epithelial components. Definitionally,<br />
the epithelial component lacks sebaceous differentiation and,<br />
instead, displays a wide range of histological differentiation. In this study,<br />
we have collected 9 cases of NSLA to characterize their histological<br />
and immunohistochemical profile.<br />
Methods. The samples were histologically reviewed, and immunohistochemical<br />
stains for CK5/6, CK7, CK14, CK18, p63, and Ki67 performed.<br />
Patients were 6 males and 3 females (mean age, 50 years).<br />
Results. All tumours were located in the parotid gland and showed<br />
intimate intermingling of lymphoid tissue with islands or strands of<br />
epithelium with a wide spectrum of histological differentiation. The<br />
immunohistochemical profiles mirrored the epithelial differentiation;<br />
hence, areas with basaloid or lymphoepithelial differentiation strongly<br />
expressed CK5/6, CK14, and p63, while areas with ductal differentiation<br />
showed strong positivity for CK18/CK7 and CK5/6/CK14/p63 in luminal<br />
and basal cell layers, respectively. A hilus structure with salivary inclusions<br />
or D2-40 (podoplanin) positive marginal sinus were identifiable in 4<br />
and 9 of the cases, respectively, confirming origin within intra-/periparotid<br />
lymph nodes. Six cases were initially misdiagnosed as other benign<br />
(n=4) or malignant tumours (n=2).<br />
Conclusions. Our study on the largest series of NSLA reported to date<br />
provides strong evidence that NSLA belongs to the group of salivary<br />
gland tumours that pathogenetically develop from embryonic salivary<br />
gland inclusions in intra-/periparotid lymph nodes. Knowledge of the<br />
wide histological spectrum of this rare and presumably un<strong>der</strong>reported<br />
tumour is important in or<strong>der</strong> to avoid misdiagnosis, particularly as malignant<br />
tumour.<br />
Der Pathologe · Supplement 1 · 2012 |<br />
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