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1.  Distinct Transcriptional Signature and Immunoprofile of CIC-DUX4–Fusion Positive Round Cell Tumors Compared to EWSR1-Rearranged Ewing Sarcomas – Further Evidence Toward Distinct Pathologic Entities 
Genes, chromosomes & cancer  2014;53(7):622-633.
Round cell sarcomas harboring CIC-DUX4 fusions have recently been described as highly aggressive soft tissue tumors of children and young adults. Due to partial morphologic and immunohistochemical overlap with Ewing sarcoma (ES), CIC-DUX4-positive tumors have generally been classified as Ewing sarcoma-like and managed similarly, however, a systematic comparison at the molecular and immunohistochemical levels between these two groups has not yet been conducted. Based on an initial observation that CIC-DUX4-positive tumors show nuclear immunoreactivity for WT1 and ETS transcription factors, FLI1 and ERG, we performed a detailed immunohistochemical and molecular analysis including these markers, to further investigate the relationship between CIC-DUX4 tumors and ES. The study group included 21 CIC-DUX4-positive sarcomas and 20 EWSR1-rearranged ES. Immunohistochemically, CIC-DUX4 sarcomas showed membranous CD99 positivity in 18 (86%) cases, but only 5 (24%) with a diffuse pattern, while WT1 and FLI1 were strongly positive in all cases. ERG was positive in 18% of cases. All ES expressed CD99 and FLI1, while ERG positivity was only seen in EWSR1-ERG fusion positive ES. WT1 was negative in all ES. Expression profiling validated by q-PCR revealed a distinct gene signature associated with CIC-DUX4 fusion, with upregulation of ETS transcription factors (ETV4, ETV1 and ETV5) and WT1, among top overexpressed genes compared to ES, other sarcomas and normal tissue. In conclusion, the distinct gene signature and immunoprofile of CIC-DUX4 sarcomas suggest a distinct pathogenesis from ES. The consistent WT1 expression may provide a useful clue in the diagnosis in the context of round cell sarcomas negative for EWSR1-rearrangement.
doi:10.1002/gcc.22172
PMCID: PMC4108073  PMID: 24723486
small blue round cell sarcoma; CIC-DUX4; WT1; Ewing Sarcoma
2.  Molecular Diagnosis of Subcutaneous Spirometra erinaceieuropaei Sparganosis in a Japanese Immigrant 
We report a case of subcutaneous sparganosis in a 68-year-old female Japanese immigrant in Germany. The patient complained of a painless erythema caudal of the umbilicus with a palpable subcutaneous cherry-sized lump. Polymerase chain reaction on formalin-fixed parasite tissue identified Spirometra erinaceieuropaei as the causative agent; the proliferative form of sparganosis, which is caused by the branching and disseminating Sparganum proliferum, could, thus, be excluded. From the excised sparganum, an immunofluorescence test was established and revealed an antibody response directed against the parasite's tegument. Histological key features of the plerocercoid that facilitate diagnosis with different stains are presented.
doi:10.4269/ajtmh.2012.12-0406
PMCID: PMC3541736  PMID: 23166198
3.  Decentral gene expression analysis for ER+/Her2− breast cancer: results of a proficiency testing program for the EndoPredict assay 
Virchows Archiv  2012;460(3):251-259.
Gene expression profiles provide important information about the biology of breast tumors and can be used to develop prognostic tests. However, the implementation of quantitative RNA-based testing in routine molecular pathology has not been accomplished, so far. The EndoPredict assay has recently been described as a quantitative RT-PCR-based multigene expression test to identify a subgroup of hormone–receptor-positive tumors that have an excellent prognosis with endocrine therapy only. To transfer this test from bench to bedside, it is essential to evaluate the test–performance in a multicenter setting in different molecular pathology laboratories. In this study, we have evaluated the EndoPredict (EP) assay in seven different molecular pathology laboratories in Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded tumors was tested in the different labs, and the variance and accuracy of the EndoPredict assays were determined using predefined reference values. Extraction of a sufficient amount of RNA and generation of a valid EP score was possible for all 70 study samples (100%). The EP scores measured by the individual participants showed an excellent correlation with the reference values, respectively, as reflected by Pearson correlation coefficients ranging from 0.987 to 0.999. The Pearson correlation coefficient of all values compared to the reference value was 0.994. All laboratories determined EP scores for all samples differing not more than 1.0 score units from the pre-defined references. All samples were assigned to the correct EP risk group, resulting in a sensitivity and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken together, the EndoPredict test could be successfully implemented in all seven participating laboratories and is feasible for reliable decentralized assessment of gene expression in luminal breast cancer.
doi:10.1007/s00428-012-1204-4
PMCID: PMC3306560  PMID: 22371223
Breast cancer; Prognosis; mRNA; Quality control

Results 1-3 (3)