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Abstract 1770 Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low grade B-cell extranodal lymphoma. The limited clinical information available in the literature makes it difficult to understand if such an indolent lymphoma may have a clinical outcome different from that observed in other extranodal marginal zone lymphomas. The aim of this study is to collect and analyze clinical characteristics of patients with primary marginal zone malignant lymphoma of the lung principally focusing on diagnosis, treatment modality, outcome and finally to evaluate biological and molecular features which may correlate with clinical behaviour. We collected clinical information and histological material on 73 patients diagnosed with marginal zone lymphoma of the lung from February 1990 to August 2008. Central pathology reviewed all histopathological material and the diagnosis was confirmed in 64 (88%) patients. The retrospective analysis has been conducted on this subset of patients. The majority of them (58/64) had limited disease at diagnosis with a good performance status (0-1) and low prognostic index (IPI 0–2). FISH analysis showed a rearrangement on 18q21 in 12 of cases. Median time from diagnosis to any treatment was 30 days (range 0–773). Twenty patients received only local treatment including definitive surgery or radiotherapy. 52 patients needed additional systemic treatment because of advanced stage or incomplete surgical resection. Most of them (26) received an alkylating containing regimen while only 10 patients were treated with an anthracycline containing regimen and 16/52 received monoclonal antibody in combination with chemotherapy. With a median follow up of 54 months, 17/64 patients (27%) relapsed. The median time to relapse was 28 months (range 1–82). No difference in terms of PFS or OS was observed among patients receiving systemic anthracycline or alkylating containing regimens. No significant correlation with MALT 1 aberrations was found. Clinical results observed in such retrospective study seem to suggest as surgery clearly benefits patients with localized disease. Chemotherapy can be reserved for early aggressive relapse. Systemic treatment could be recommended for patients with advanced stage or with incomplete response after the surgical procedure: when chemotherapy must be considered, alkylating containing regimens seem the best option. Considering data of a “pre-rituximab era”, the role of monoclonal antibodies still needs to be clarified and ongoing trials from IELSG could be helpful on this topic. Disclosures: No relevant conflicts of interest to declare.

HISTORY AND ADMISSION FINDINGS More than two years after unrelated stem cell transplantation with ongoing immunosuppressive therapy due to chronic graft-versus-host disease a patient was admitted with dyspnea. In the sequel, the patient developed ptosis. DIAGNOSIS CT scan of paranasal sinus demonstrated an orbita-infiltrating tumor identified as mucormycosis by microbiology and biopsy. Further diagnostics showed cerebral involvement. Due to additional pancytopenia a conservative approach to this rhino-orbito-cerebral mucormycosis was chosen. TREATMENT AND COURSE With dose intensive liposomal amphotericin B and posaconazol maintenance therapy stabilization followed by continuously regression was achieved. CONCLUSION Infections with mucorales have a low incidence, though due to rapid progression and high mortality they should be included into diagnostic considerations. Diagnosis is confirmed by biopsy and therapy is primarily operative. Systemic therapy is targeted to eliminate underlying risk factors (cytopenia, immunosuppression, ketoacidosis, iron overload) and application of effective antimycotics as mono- or combined therapy.

Glasverkapselte SAMs (SAM: selbstorganisierte Monoschicht) auf durchstimmbaren Au/Ag-Nanoschalen werden von S. Schlucker et al. in der Zuschrift auf S. 1984 ff. vorgestellt. Diese Systeme haben ein groses Potenzial als Marker fur die oberflachenverstarkte Raman-Streuung (SERS) in bioanalytischen und biomedizinischen Anwendungen, die auf einer Anregung mit rotem Laserlicht beruhen, z. B. in Assays und der Mikroskopie. Die Methode kombiniert die spektroskopischen Vorteile von SAMs mit der Stabilitat einer Glashulle.

21025 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with incompletely understood pathogenesis and poor prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been demonstrated in several tumors and is partly associated with a more aggressive phenotype and a worse prognosis. In addition, targeting the EGFR tyrosine kinase represents a successful new therapeutic strategy, e.g. in non-small cell lung cancer. Therefore, we investigated the role of EGFR in ACC as a potential therapeutic target. Methods: EGFR expression was analyzed by immunohistochemistry in 115 ACCs and 5 normal adrenals using paraffin sections and tissue arrays (scoring of expression: 0–3). Utilizing the clinical data from the German ACC registry, Kaplan Meier survival analyses were performed. In 30 patients the tumor DNA was sequenced for mutations of the “hot spot” exons 19–21 of the EGFR gene. In addition, cells of the ACC cell line NCI-h295 were incubated with the EGFR antibody cetuximab (1–100 μg/ml) and cell proliferation was measured by MTT tests. Results: Immunohistochemistry revealed EGFR expression in 78% of ACCs. In 67/115 (58%) of the ACCs and 0/5 of the normal adrenals the expression level was judged as moderate-to-high (score 2 or 3). However, the expression level did not correlate with the clinical outcome in these patients. In addition, none of the sequenced tumor DNA samples showed a mutation in exons 19–21. Cetuximab exhibited a dose dependent antiproliferative effect in NCI-H295 cells (cell viability: 1μg/ml: 95±2%; 10μg/ml 90±3%*; 100 μg/ml 85±4%* vs untreated control cells: 100±3%; * = p No significant financial relationships to disclose.

In most mature B-cell non-Hodgkin lymphoma (NHL) chromosomal translocations result in the transcriptional deregulation of an oncogene by juxtaposing it to regulatory sequences of genes that are constitutively expressed in mature B cells, most often the Ig genes. Recently, a novel recurrent translocation t(3;14)(p13;q32) that results in deregulation of the FOXP1 forkhead transcription factor has been reported in a variety of B cell lymphoma. Here we present the analysis of 275 B-cell NHL: 102 diffuse large B cell lymphoma (DLBCL) (49 nodal and 53 extranodal cases) 122 marginal zone lymphoma (MZL) from different localization (cutenous n= 9, salivary gland n= 13, pulmonary n=50, ocular adnexae n=36, thyroid n=8, gastric n=6), 30 follicular lymphoma (FL) and 21 mantle cell lymphoma (MCL). The presence of genetic aberrations involving the FOXP1 gene was studied by interphase fluorescence in situ hybridization (FISH) and FOXP1 protein expression - by immunohistochemistry using the JC12 monoclonal antibody. In total, 5 of 275(2%) lymphoma were found to carry a chromosomal breakpoint within the FOXP1 gene. Further FISH studies indicated the presence of a FOXP1/IgH translocation in only 2 of these samples, suggesting the likely involvement of other translocation partner. All samples that harbored a FOXP1 breakpoint represented aggressive B cell lymphoma with proliferation fraction of 70–90% defined by the Ki 67% labeling pattern. Cytogenetic analysis and/or FISH suggested a presence of the complex chromosomal rearrangements. Four of 5 tumors presented at extranodal sites: gastro-intestinal tract (N=3); thyroid gland (N=1). All samples expressed B-cell markers and lacked CD5 and CD10 - a phenotype consistent with a marginal zone derivation. Interestingly, we failed to identify a FOXP1 breakpoint in any of the “true” low grade MZL in our series. A gain of genomic material was found in 80 (29%) of these samples, indicated by detection of more than two FISH signals in a variable number of cells and/or cytogenetic data. In the vast majority of these cases trisomy 3 was further identified. All 5 samples that harbor FOXP1 chromosomal breakpoint showed strong nuclear labeling pattern when stained with JC12 monoclonal antibody. FOXP1 nuclear expression, in a variable number of the cells was detected in 95% of the cases with genomic gain/trisomy 3, however also in 40 % of the samples without evidence of any genetic aberrations in this locus, suggesting a range of mechanisms, regulating the FOXP1 expression.

Background & Aims The intestinal microbiota is an important determinant of the mucosal response. In patients with inflammatory bowel diseases, the mucosal immune system has inappropriate interactions with the intestinal microbiota. We investigated how the composition of the intestinal microbiota affects its endotoxicity and development of colitis in mice. Methods Germ-free C57BL/6J-Rag1tm1Mom (Rag1−/−) mice were colonized with 2 different types of complex intestinal microbiota. Colitis was induced in Rag1−/− mice by transfer of CD4+CD62L+ T cells from C57BL/6J mice. Colonic tissues were collected and used for histologic analysis and cell isolation. Activation of lamina propria dendritic cells and T cells was analyzed by flow cytometry. Results After transfer of CD4+CD62L+ T cells, mice with intestinal Endolo microbiota (a low proportion of Enterobacteriaceae, high proportion of Bacteroidetes, and low endotoxicity) maintained mucosal immune homeostasis, and mice with highly endotoxic Endohi microbiota (a high proportion of Enterobacteriaceae and low proportion of Bacteroidetes) developed colitis. To determine whether the effects of Endohi microbiota were related to the higher endotoxic activity of lipopolysaccharide (LPS), we compared LPS from Enterobacteriaceae with that of Bacteroidetes. Administration of Escherichia coli JM83 (wild-type LPS) to the mice exacerbated colitis, and Escherichia coli JM83 + htrBPG (mutated LPS, with lower endotoxicity, similar to that of Bacteroidetes) prevented development of colitis after transfer of the T cells to mice. Conclusions The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis after transfer of CD4+CD62L+ T cells. This finding might aid the design of novel biologics or probiotics to treat inflammatory bowel disease.

Background “Quorum sensing” (QS) is the phenomenon which allows single bacterial cells to measure the concentration of bacterial signal molecules. Two principle different QS systems are known, the Autoinducer 1 system (AI-1) for the intraspecies communication using different Acyl-homoserine lactones (AHL) and AI-2 for the interspecies communication. Aim of this study was to investigate QS of Escherichia coli Nissle 1917 (Mutaflor). Results While E. coli Nissle is producing AI-2 in a density dependent manner, no AI-1 was produced. To study the effect of AI-2 in the DSS (dextran sulphate sodium) induced mouse model of acute colitis, we silenced the corresponding gene luxS by intron insertion. The mutant bacterium E. coli Nissle::luxS was equally effective in colonizing the colon and the mutation turned out to be 100% stable during the course of the experiment. Isolating RNA from the colon mucosa and performing semiquantitative RT PCR, we were able to show that the expression of the pro-inflammatory cytokine IFN-y was suppressed in mice being infected with the E. coli Nissle wild type. Mice infected with the E. coli Nissle::luxS mutant showed a suppressed expression of IL-10 compared to uninfected mice, while the expression of the pro-inflammatory cytokines IL-6 and TNF-α was higher in these mice. The expression of mBD-1 was suppressed in mice being infected with the mutant in comparison to the mice not infected or infected with the wild type. No differences were seen in the histological examination of the colon sections in the different groups of mice. Conclusions E. coli Nissle is producing AI-2 molecules, which are influencing the expression of cytokines in the mucosa of the colon in the DSS mice. However, if QS has a direct influence on the probiotic properties of E. coli Nissle remains to be elucidated.