Sex ratio biases in termites provide evidence for kin selection

Contains fulltext : 142755.pdf (publisher's version ) (Closed access)Molecular testing of tumor samples to guide treatment decisions is of increasing importance. Several drugs have been approved for treatment of molecularly defined subgroups of patients, and the number of agents requiring companion diagnostics for their prescription is expected to rapidly increase. The results of such testing directly influence the management of individual patients, with both false-negative and false-positive results being harmful for patients. In this respect, external quality assurance (EQA) programs are essential to guarantee optimal quality of testing. There are several EQA schemes available in Europe, but they vary in scope, size and execution. During a conference held in early 2012, medical oncologists, pathologists, geneticists, molecular biologists, EQA providers and representatives from pharmaceutical industries developed a guideline to harmonize the standards applied by EQA schemes in molecular pathology. The guideline comprises recommendations on the organization of an EQA scheme, defining the criteria for reference laboratories, requirements for EQA test samples and the number of samples that are needed for an EQA scheme. Furthermore, a scoring system is proposed and consequences of poor performance are formulated. Lastly, the contents of an EQA report, communication of the EQA results, EQA databases and participant manual are given

Lymphoproliferative Erkrankungen des weiblichen und männlichen Genitaltrakts sowie der Mamma

Sowohl das weibliche als auch das männliche Genitalsystem zeichnen sich durch einen organtypischen Befall durch maligne Lymphome aus, was sowohl für die primär dort entstehende Lymphomerkrankung als auch für die sekundär metastatische Beteiligung systemischer Lymphome zutrifft. Das Kapitel gibt auf dem Boden der in der WHO Klassifikation definierten Entitäten eine umfassende Besprechung und Differenzialdiagnose des nach anatomischen Abschnitten gegliederten Genitalsystems mit den zum Teil sehr wichtigen organotypischen Differenzialdiagnosen. Eine besondere Beachtung finden die Lymphom-ähnlichen Läsionen des Uterus, deren Diagnose und Abgrenzung zu einem Befall durch ein NHL große Bedeutung besitzt. In einem weiteren Kapitel werden die seltenen primären NHL der Mamma besprochen und das besondere anaplastisch großzellige Lymphom assoziiert zu Silikon Implantaten dargestellt und in Klinik und Prognose diskutiert

Diagnostische Strategien, Immunhistochemie und molekulare Diagnostik lymphatischer Gewebe

Das Kapitel gibt eine präzise Übersicht über die Grundlagen der modernen Diagnostik der pathologischen Gewebeuntersuchung lymphatischer Läsionen. Dabei werden die Säulen einer relevanten Krankheitsdefinition, die Morphologie, Immunhistochemie, molekulare Genetik und Klinik und deren methodische Voraussetzungen für die Problemstellungen im Einzelnen herausgestellt und an praktischen Beispielen diskutiert

Lymphoproliferative Erkrankungen der Niere und ableitenden Harnwege

Primäre Lymphome sind in den Nieren und ableitenden Harnwegen sehr selten. Das Kapitel bietet eine aktuelle Literaturübersicht und einen Erfahrungsbericht zu diesen Krankheiten und zeigt die organtypischen Befallsmuster der verschiedenen anatomischen Abschnitte des ableitenden Harnweg-Systems

Role of immunohistochemistry and fluorescence in-situ hybridization (FISH) in the diagnosis of spindle and round cell tumors of the kidney

Spindle cell/mesenchymal tumors of the kidney are rare. The diagnosis is supported mainly by the application of ancillary techniques such as immunohistochemistry (IH) and in-situ hybridization (FISH). An accurate diagnosis is essential because early management by complete resection and adjuvant chemotherapy improves the prognosis dramatically. Synovial sarcoma and primitive neuroectodermal tumor/Ewing sarcoma are infrequent malignancies which usually present in soft tissues but rarely in the kidney. The challenge for the pathologists is to histologically differentiate between different types of sarcomas such as PNET/Ewing’s sarcoma, sarcomatous dedifferentiated renal cell carcinoma, metastasis, non-Hodgkin’s lymphoma, nephroblastoma and angiomyolipoma. Methods: We report from our experience six exemplary rare cases that presented in the kidney as spindle/round cell tumors. Results: We have arrived at the accurate diagnosis after performing a large panel of IH and FISH. Conclusion: In summary we advise an immunohistochemical panel for round/spindle cell tumors of the kidney and for unclear cases we advise to add (FISH) to get the correct diagnosis, as they are completely different regarding surgical approach and post-operative adjuvant therapy

Supplementary Material for: Hypoxia Induces Mesenchymal Gene Expression in Renal Tubular Epithelial Cells: An in vitro Model of Kidney Transplant Fibrosis

<b><i>Background:</i></b> The development of interstitial fibrosis and tubular atrophy is a common complication after kidney transplantation and is associated with reduced long-term outcome. The hallmark of tubulointerstitial fibrosis is an increase in extracellular matrix resulting from exaggerated activation of fibroblasts/myofibroblasts, and tubular atrophy is characterized by a decrease in tubular diameter and loss of function. Atrophic epithelial cells may undergo epithelial-to-mesenchymal transition (EMT) with potential differentiation into interstitial fibroblasts. One potential driver of EMT in developing interstitial fibrosis and tubular atrophy is chronic hypoxia. <b><i>Methods:</i></b> The expression of 46 EMT-related genes was analyzed in an in vitro hypoxia model in renal proximal tubular epithelial cells (RPTEC). Furthermore, the expression of 342 microRNAs (miR) was evaluated in hypoxic culture conditions. <b><i>Results:</i></b> Hypoxic RPTEC expressed markers of a more mesenchymal phenotype and showed an increased expression of matrix metalloproteinase-2 (MMP2). MMP2 expression in RPTEC correlated inversely with a decreased expression of miR-124, which was found to have a putative binding site for the MMP2 transcript. Overexpression of miR-124 inhibited MMP2 protein translation. Hypoxia was associated with increased migration/proliferation of RPTEC which was reversed by miR-124. <b><i>Conclusions:</i></b> These results indicate that hypoxia promotes a mesenchymal and migratory phenotype in renal epithelial cells, which is associated with increased MMP2 expression. Hypoxia-dependent MMP2 expression is regulated via a reduced transcription of miR-124. Overexpression of miR-124 antagonizes hypoxia-induced cell migration. Further research is needed to elucidate the functional role of miR-124 and MMP2 in the development of fibrosis in renal transplant degeneration

HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing.

Trastuzumab-based therapy has been shown to confer overall survival benefit in HER2-positive patients with advanced gastric cancer in a large multicentric trial (ToGA study). Subgroup analysis identified adenocarcinomas of the stomach and gastroesophageal (GE) junction with overexpression of HER2 according to immunohistochemistry (IHC) as potential responders. Due to recent approval of trastuzumab for HER2 positive metastatic gastric and GE-junction cancer in Europe (EMEA) HER2 diagnostics is now mandatory with IHC being the primary test followed by fluorescence in situ hybridization (FISH) in IHC2+ cases. However, in order to not miss patients potentially responding to targeted therapy determination of a HER2-positive status for gastric cancer required modification of scoring as had been proposed in a pre-ToGA study. To validate this new HER2 status testing procedure in terms of inter-laboratory and inter-observer consensus for IHC scoring a series of 547 gastric cancer tissue samples on a tissue microarray (TMA) was used. In the first step, 30 representative cores were used to identify specific IHC HER2 scoring issues among eight French and German laboratories, while in the second step the full set of 547 cores was used to determine IHC HER2 intensity and area score concordance between six German pathologists. Specific issues relating to discordance were identified and recommendations formulated which proved to be effective to reliably determine HER2 status in a prospective test series of 447 diagnostic gastric cancer specimens