This so-called "ALK-Harmonization-Study" shows for the first time that predictive semiquantitative IHC reveals reliable and reproducible results across several labs when methodology and interpretation are strictly defined and the pathologists are uniquely trained. The application of validated ALK IHC assays and its comparison to ALK-FISH is highly needed in future clinical trials. This might answer the question if ALK-IHC cannot only serve as a prescreening tool, but as a stand-alone test at least in cases displaying an unequivocally staining pattern as well as an alternative predictive test in samples with reduced FISH interpretability.

Infection of human cells by the obligate intracellular bacterium Chlamydia trachomatis requires adhesion and internalization of the infectious elementary body (EB). This highly complex process is poorly understood. Here, we characterize Ctad1 (CT017) as a new adhesin and invasin from C. trachomatis serovar E. Recombinant Ctad1 (rCtad1) binds to human cells via two bacterial SH3 domains located in its N-terminal half. Pre-incubation of host cells with rCtad1 reduces subsequent adhesion and infectivity of bacteria. Interestingly, protein-coated latex beads revealed Ctad1 being an invasin. rCtad1 interacts with the integrin β1 subunit on human epithelial cells, and induces clustering of integrins at EB attachment sites. Receptor activation induces ERK1/2 phosphorylation. Accordingly, rCtad1 binding to integrin β1-negative cells is significantly impaired, as is the chlamydial infection. Thus interaction of C. trachomatis Ctad1 with integrin β1 mediates EB adhesion and induces signaling processes that promote host-cell invasion.

In a previous study, we reported that the OmcB protein from Chlamydia pneumoniae mediates adhesion of the infectious elementary body to human HEp-2 cells by interacting with heparin/heparan sulfate-like glycosaminoglycans (GAGs) via basic amino acids located in the first of a pair of XBBXBX heparin-binding motifs (K. Moelleken and J. H. Hegemann, Mol. Microbiol. 67:403-419, 2008). In the present study, we show that the basic amino acid at position 57 (arginine) in the first XBBXBX motif, the basic amino acid at position 61 (arginine) in the second motif, and another amino acid (lysine 69) C terminal to it play key roles in the interaction. In addition, we show that discrimination between heparin-dependent and -independent adhesion by C. trachomatis OmcBs is entirely dependent on three variable amino acids in the so-called variable domain C terminal to the conserved XBBXBX motif. Here, the predicted conformational change in the secondary structure induced by the proline at position 66 seems to be crucial for heparin recognition. Finally, we performed neutralization experiments using different anti-heparan sulfate antibodies to gain insight into the nature of the GAGs recognized by OmcB. The results suggest that C. trachomatis serovar L2 OmcB interacts with 6-O-sulfated domains of heparan sulfate, while C. pneumoniae OmcB apparently interacts with domains of heparan sulfate harboring a diverse subset of O-sulfations.

Lung-sparing RP for IMIG stage III MPM is feasible and offers promising long-term survival. The tumour spread at the resected previous incisions is associated with more incomplete resections and was a negative prognosticator for long-term survival. The tumour spread at the resected previous incisions or chest tube sites should be considered as T4 or stage IV according to the IMIG staging system.