Comprehensive Profiling of Metaplastic Breast Carcinoma Reveals Frequent Over-Expression of PD-L1

Background: Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy relative to usual breast carcinomas such as ductal and lobular subtype. In molecular terms, MBC usually clusters with triple negative breast cancers (TNBC), but MBCs portray a worse prognosis in comparison with TNBC. Published studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. Methods: 297 samples [MBC (n=75), triple-negative breast cancer of no-special-type (TNBC-NOS, n=106), HER2-positive breast cancers (n=32) and luminal breast cancers (n=84)] were profiled using direct sequencing analysis [Illumina MiSeq Next Generation Sequencing (NGS)]. Immunohistochemistry for PD-L1 (SP142, Spring Bioscience) and PD-1 (NAT105, Ventana) was performed using automated procedures. Results: 89% MBCs exhibited triple-negative immunophenotype (ER-/PR-/HER2-). The most common mutations in MBCs included TP53 (67%) and PIK3CA mutations (23%). Other mutations were rare including HRAS mutations (7%), STK11 (5%), FBXW7, PTEN, c-MET and JAK3 (4%, respectively). PD-L1 expression on cancer cells was detected in significantly higher proportion of MBCs (46%) than in other molecular subtypes (6% in luminal and HER2+ breast cancers, respectively and 9% in TNBC-NOS, p\u3c0.001). PD-1 positive tumors infiltrating lymphocytes (TILs) varied greatly in MBCs (0 to \u3e50/mm2). Conclusion: Comprehensive profiling of a large cohort of this rare carcinoma highlighted predominance of TP53 mutations, wild type EGFR gene expression, a distinct increase in proportion of PD-L1 expression in carcinoma cells, and PD-1 expression in TILs. The latter propert

Dermacentor reticulatus: a vector on the rise

Dermacentor reticulatus is a hard tick species with extraordinary biological features. It has a high reproduction rate, a rapid developmental cycle, and is also able to overcome years of unfavourable conditions. Dermacentor reticulatus can survive under water for several months and is cold-hardy even compared to other tick species. It has a wide host range: over 60 different wild and domesticated hosts are known for the three active developmental stages. Its high adaptiveness gives an edge to this tick species as shown by new data on the emergence and establishment of D. reticulatus populations throughout Europe. The tick has been the research focus of a growing number of scientists, physicians and veterinarians. Within the Web of Science database, more than a fifth of the over 700 items published on this species between 1897 and 2015 appeared in the last three years (2013–2015). Here we attempt to synthesize current knowledge on the systematics, ecology, geographical distribution and recent spread of the species and to highlight the great spectrum of possible veterinary and public health threats it poses. Canine babesiosis caused by Babesia canis is a severe leading canine vector-borne disease in many endemic areas. Although less frequently than Ixodes ricinus, D. reticulatus adults bite humans and transmit several Rickettsia spp., Omsk haemorrhagic fever virus or Tick-borne encephalitis virus. We have not solely collected and reviewed the latest and fundamental scientific papers available in primary databases but also widened our scope to books, theses, conference papers and specialists colleagues’ experience where needed. Besides the dominant literature available in English, we also tried to access scientific literature in German, Russian and eastern European languages as well. We hope to inspire future research projects that are necessary to understand the basic life-cycle and ecology of this vector in order to understand and prevent disease threats. We conclude that although great strides have been made in our knowledge of the eco-epidemiology of this species, several gaps still need to be filled with basic research, targeting possible reservoir and vector roles and the key factors resulting in the observed geographical spread of D. reticulatus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1599-x) contains supplementary material, which is available to authorized users

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)