Evidence suggests that microbiota may contribute to the pathogenesis of several diseases, including cancer. In the case of bladder cancer, preliminary studies have found alterations in the urinary microbiota of patients with urothelial carcinoma compared with healthy individuals. Conversely, the urinary microbiota differ between men and women, and it has been hypothesized that these differences are associated with the lower incidence of bladder cancers in women. The objective of this study was to characterize the bladder microbiota in paired samples of tumor and non-tumor mucosa of patients with malignant bladder neoplasia using next-generation sequencing. In addition, we aimed to study potential differences in microbial composition in tumor samples according to clinical and pathological variables, and to determine possible microbial profiles. We found significant differences in microbial richness at the genus level, with a higher richness observed in the non-tumor compared with the tumor mucosa. It was also shown that Actinobacteria were significantly more enriched in the non-tumor compared with the tumor mucosa (P = 0.014). In the multivariate analysis, we found significant differences in microbial composition according to tumor grade (P = 0.03 and 0.04 at the phylum and genus levels, respectively). Moreover, we detected a higher microbial richness in non-tumor vs. tumor tissues which agrees with the global assumption that microbial richness is an indicator of health. The greater abundance of members of the Actinobacteria phylum in the non-neoplastic bladder mucosa samples supports the hypothesis that a higher abundance of Actinomycetes is associated with a lower rate of bladder cancer in women and suggests a protective role for these microbiota. We detected a microbial profile that was enriched for Enterococcus in low-grade tumors. Finally, we identified the presence of two clusters in the microbial composition of the tumor mucosa samples, significantly enriched for the genera Barnesiella, Parabacteroides, Prevotella, Alistipes, and Lachnospiracea_incertae_sedis (Cluster 1), or Staphylococcus (Cluster 2). Further longitudinal studies are needed to assess the role of the bladder microbiota in carcinogenesis.

e17116 Background: The characterization and prognostic relevance of immune cells in the tumor microenvironment of endometrial cancer (EC) remain unknown. Our aims are to analyze the presence of tumor infiltrating lymphocytes (TIL) and peritumoral lymphocytes (PTL) in tumoral tissue of patients with EC, and to identify the correlation between TILs and PTLs subsets with clinicopathologic features and its prognostic value Methods: CD3, CD4, CD8, CD20, and FOXP-3 was determined by immunohistochemestry (IHQ). A 4-point score was defined based on TIL counts per highpowered field: (negative, low, moderate, and high). We used 10% positive peritumoral lymphocytes as a low-high cutoff value. POLE mutation was identified by Sanger sequencing of the exonuclease domain (exons 9-14). Analysis of mismatch repair expression and TP53 gene mutation status were assessed. Results from IHQ and analysis mutation were correlated with clinicopathological parameters and survival. Results: We recovered tumor samples from 68 FIGO stage I–IV EC patients. POLE mutations were identified in 5 of 44 (11.4%) EC analyzed. Microsatellite instability (MSI) and TP53 mutation were found in 45% and 25 % of cases respectively. According PTL, MSI tumors were significantly associated with low CD4+ (p = 0.01). High CD8+ was significantly associated with endometrioid grade 1-2 tumors (p = 0.04). Low FOXP3+ was significantly associated with endometrioid grade 1-2 (p = 0.02), MSS tumors (p < 0.01), FIGO stage I-II (p < 0.01), POLE WT (p < 0.01), TP53 WT (p < 0.01), and negative lymphovascular space invasion (p < 0.01). Negative CD20+ TIL was associated with endometrioid grade 1-2 tumors (p < 0.01) and ≥50% myometrial invasion (p = 0.03). Moderate CD8+ TIL was associated with lower tumor stage (p = 0.01). High CD8+ TIL was associated with better 5-year overall survival (OS) rate (high: 100 % vs. low: 53%; p = 0.003). No significant association was observed between POLE status, TP53 status, MMR expression and survival. Conclusions: Regulatory and cytotoxic T cells subsets differs in EC patients. High CD8+ TILs was significantly associated with better 5-year OS.

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e17113 Background: There are unmet needs for targeted therapy in Endometrial Cancer (EC). The integrated genomic characterization of EC provided insights into disease biology. Our primary objective is to identify potential actionable pathways to target therapeutically in EC according to the microsatellite status (microsatellite instability high = MSI-H, and microsatellite stable/microsatellite instability low = MSS/MSI-L). Methods: 375 RNAs from the genomic profile of EC within the TCGA database were used to perform RNA-seq analysis. We analyzed RNA-sequencing data with edgeR package to filter and normalize the data, followed by the limma package with its Voom method, linear modeling and empirical Bayes moderation to asses differential expression. Reactome FI Cytoscape app was used to perform pathway and network-based data analysis. Results: According to the microsatellite status, two groups were identified: Group 1 = MSI-H (127 patients) and Group 2 = MSS/MSI-L (248 patients). Significant expression differences were found in 2141 genes. In the Group 1 we identified 1194 genes overexpressed and 947 genes overexpressed in the Group 2. Group 1 includes genes associated with cell proliferation. Group 2 includes genes associated with genomic instability and apoptosis evasion (table 1). Conclusions: In EC patients, Cyclin-dependent kinase (CDK) pathways could be a potential therapeutic target, especially in patients with MSI-H tumors. Further studies are necessary in order to evaluate the activity of CDKs inhibitors in this population.[Table: see text]