At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).

Circulating microRNAs (miRNAs) are promising non-invasive biomarkers whose expression may be affected by confounding factors, including hemolysis, that should be considered in studies of miRNA discovery. The present study proposes a methodology for evaluating the impact of hemolysis on the expression of miRNAs. An experiment of controlled hemolysis was designed for assessing if changes in the expression of eight miRNAs observed to be circulating in plasma may be associated with hemolysis, and also to estimate the level of red blood cell (RBC) contamination in plasma samples where the expression of these miRNAs will be measured. It was confirmed that four miRNAs, miR-16, miR-92a, miR-451 and miR-486, known to be present in blood cells, were influenced by contamination of RBCs. Furthermore, it was demonstrated that miR-378 and miR-30c are hemolysis-independent and that the expression of miR-320 and miR-324-3p was associated with the level of RBC contamination. This procedure is proposed as a tool for the evaluation of the influence of hemolysis on candidate circulating miRNA biomarkers prior to their analysis in plasma samples.

This preoperative chemotherapy is feasible and can also be proposed for selected elderly patients. Grade 3 or 4 hematologic toxicity was common, but DI was excellent. Concurrent preoperative RT is safe, although an increased rate of grade 4 thrombocytopenia and limited increase in wound complications may be observed.

Desmoid‐type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β‐catenin mutations (S45F) appeared to be related to this higher risk compared to T41A‐mutated or wild‐type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β‐catenin for α‐catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n = 14), S45F (n = 10), or WT (n = 9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel, and assessment of immune system‐based biomarkers by immunohistochemistry. Mutated proteins were more stable than WT and formed a weaker complex with α‐catenin. Consensus unsupervised gene clustering revealed the presence of two DF group‐mutated (T41A + S45F) and WT (P = 0.0047). The gene sets ‘Inflammatory‐Defense‐Humoral Immune Response’ and ‘Antigen Binding’ were significantly enriched in T41A. The deregulation of 16 inflammation‐related genes was confirmed. Low numbers of T cells and tumor‐associated macrophages (TAM) infiltrating the tumors and low/absent PD‐1/PD‐L1 expression were also identified. We demonstrated that mutated DFs (T41A or S45F) and WT are two distinct molecular subgroups with regard to β‐catenin stability, α‐catenin affinity, and gene expression profiling. A different inflammation signature characterized the two mutated groups, suggesting mediation either by T41A or by S45F. Finally, all mutated cases showed a low number of TIL and TAM cells and a low or absent expression of PD‐1 and PD‐L1 consistent with β‐catenin activation insensitive to checkpoint blockade.

No abstract

Circulating tumour cells (CTC) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer (BC) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect (AT) and ScreenCell®Cyto (SC) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic (M0) and 47 metastatic (M+) BC patients, at baseline (T0) and during treatment (T1). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases (57.4% versus 25%, p = 0.041). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 (median (interquartile range, IQR): 0.18 (0.07–0.42) versus 0.84 (0.33–1.84), p = 0.005) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently (25% versus 8%) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts.

No abstract

This report highlights the need to add a technical validation step to the high-throughput-based miRNA identification workflow, after their discovery and before the validation step in an independent series.