Verhandlungen der Deutschen Gesellschaft fur Pathologie最新文献

GIPC is highly expressed in human pancreatic adenocarcinoma and is a central protein for the stability of IGF-1R in pancreatic adenocarcinoma cell lines (15). The goal of this study was to prove the importance of GIPC in vivo and to evaluate possible therapeutic strategies that target this protein and its PDZ domain. In vivo effects of GIPC knockout were studied after lentiviral transduction of luciferase-expressing MiaPaCa2 pancreatic cancer cells with shRNA against GIPC; growth characteristics were monitored with bioluminiscence. Knockdown of GIPC led to a significant inhibition of pancreatic tumor cell growth in vivo in different mouse models. To test a possible therapeutic approach, the PDZ domain of GIPC was targeted by a short peptide composed of the amino acid sequence PSQSSSEA. This octapeptide was designed based on the C-terminal binding motif of GAIP. Targeting GIPC with this peptide inhibited the association between IGF-1R and GIPC. The subsequent downregulation of IGF-1R decreased proliferation in vitro and in vivo. In conclusion, our findings suggest that targeting GIPC and its PDZ domain-mediated interaction with the tyrosine kinase receptor IGF-1R could be a promising new treatment option for pancreatic cancer.

Various microsatellite and CGH studies in prostate cancer identify deletions on the short arm of chromosome 8 especially at band 8p21-22 searching for unknown putative tumor suppressor genes. By means of microsatellite markers several candidate genes were detected which may play different roles in early prostate cancer progression. We established a quantitative gene dosage PCR based on the real time PCR method serving the purpose of genomic fine mapping. Therefore we used 10 Assays-on Demand (ABI) for the detection of deletions located between and nearby the microsatellite markers D8S258 and NEFL spanning a genomic region of approximate 7 mbp. Comparative immunohistochemical analysis from tissue micro arrays (TMA) of 1122 independent cases followed. We were able to detect three clearly separated deletion intervals on 8p21-22. One on LZTS1, second on NEFL and third a deletion hot spot on LOXL2, which was affected in 72% of all investigated cases. Our comparative immunohistochemical TMA based studies demonstrate that LOXL2 is nearly lost in most prostate cancer tissues. LOXL2 catalyze the crosslinking of collagen and elastin in the extracellular matrix and it has been assumed that it is involved in tumor suppression and cell adhesion. LOXL2 is frequently expressed in proliferating tissues and shows a high expression in benign prostate tissue too. In prostate cancer the expression is positive correlated with the MIB1-score.

The intraoperative evaluation of sentinel lymph nodes is an ongoing debated issue. In this review we discuss different approaches to sentinel lymph node processing in an intra operative setting and in the consecutive embedding in paraffin. We propose a method, which uses routine intra operative examination of lymph nodes with stereo microscopy with selected frozen section analysis. We demonstrate preliminary data on a larger patient collective along with data on a control group. We could show in our study that a higher rate of metastates can be achieved avoiding intra operative frozen sections on grossly inconspicuous sentinel lymph nodes.

Inbred strains are the raw material for the generation of Genetically Engineered Mice (GEM) that have become indispensable tools for cancer research, and for the identification of genes involved in human diseases. The "German Mouse Clinic" was designed to provide the scientific community with a systematic, standardized and comprehensive phenotyping of mouse models on various genetic backgrounds and generated by different methods (transgenic, knockouts, ENU mutagenesis screen and gene-trap approaches). The pathology screen within the German Mouse-Clinic was conceived to ensure a complete morphologic phenotype of mouse models, to support discovery of genes functions, and to understand how these genes influence the development of human diseases. The goal is to define disease entities that can be recognized by a pathologist and relate them to human disorders when possible. Knowing the inherent morphologic phenotype of the most frequent used mouse strains is of utmost importance for the correct interpretation of mouse models. The main challenges, which pathologist are confronted to validate mouse models for human diseases include (1) knowledge of mouse biology and of histological differences between mouse strains and humans, (2) the terminology that should be used for the classification of neoplastic lesions in GEM's, (3) to asses the usefulness of a particular GEM as model for a human disease.

The primary round cell tumors of the skeletal system focus on the differential diagnosis of Ewing sarcoma. It is known that this tumor can be defined on the basis of translocation 11; 22. Therefore, in most cases, the differential diagnosis to other "round cell" tumors of the skeletal system no longer causes great problems. Besides the differential diagnosis of chondrogenic tumors, the diagnosis of osteoid-forming tumors is very problematic histologically. Focus of attention is the diagnosis of highly malignant osteosarcoma. This must be differentiated from the low malignant, intramedullary osteosarcomas, as well as from benign, osteoid-forming tumors and -like tumors. Especially the tumors located at the border between highly malignant osteosarcoma and benign osteoblastoma are difficult as far as the differential diagnosis is concerned. These cases are so rare that they are dealt with only at a casuistic level. Therefore, with regard to their classification, there have been almost no changes recently.