The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome-wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest-PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptasequantitative polymerase chain reaction, and immunohistochemistry, respectively.HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12-p11.2 and 14q32.33, where Abbreviations: aCGH, array comparative genomic hybridization; CNA, copy number alteration; Cq, quantification cycle; FFPE, formalin-fixed paraffin-embedded; HPV, human papiloma virus;HrHPV, High risk HPV; IHCi, mmunohistochemistry; PCR, polymerase chain reaction; PeCa, penile cancer; qPCR, quantitative polymerase chain reaction; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; TMA, tissue microarray. ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641-2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti-EGFR and anti-COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV-associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa. K E Y W O R D Scarcinoma of the penis, genomic alterations, human papillomavirus, molecular markers

factors, the diagnosis is delayed (Gao et al., 2016). Consequently, patients are usually diagnosed at an advanced stage, resulting in total or partial penectomy, and often present with regional lymph node metastasis and reduced survival (

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Background: Recent studies have found an association between Helicobacter pylori infection and prediabetes. Whether H. pylori per se or host factors are involved in the disturbance of glycated hemoglobin needs further investigation. The aim of this study was to determine the association of glycated hemoglobin levels with endoscopic diagnosis and the inflammatory response in H. pylori infection. Methods: A cross-sectional study was carried out in 88 dyspeptic non-diabetic adults who underwent esophagogastroduodenoscopy. The diagnosis of H. pylori infection was performed through urease test and histopathological exam. Cases were initially distributed into two groups: control (without H. pylori infection, n = 22) and HP (patients with H. pylori infection, n = 66). HbA1c was measured to determine prediabetes status according to the American Diabetes Association criteria, and then the groups were subdivided into non-prediabetic (n = 14), prediabetic (n = 8), non-prediabetic HP (n = 26) and prediabetic HP (n = 40) groups. Gastric mucosa was histologically evaluated to determine H. pylori density and inflammatory activity according to Sydney System. To investigate the balance of anti-inflammatory and pro-inflammatory cytokines we measured interleukin 10 (anti-inflammatory) and Tumor Necrosis Factor-a (proinflammatory) in the plasma or in the gastric mucosa. Results: Patients with H. pylori infection had higher mean HbA1c levels than those without H. pylori infection. However, increased HbA1c levels were not associated with H. pylori-related factors but with the bacterial density, the intensity of inflammation and the activity of the chronic gastritis. In addition, H. pylori infection per se did not alter

Background: Human papillomavirus (HPV) infection is a risk factor for penile cancer (PC). The miR-145 expression has been correlated to this virus genomic amplification. In this context, this work aims to determine the expression level of miR-145 in penile tumors infected by high-risk HPV and correlate it with the clinicopathological characteristics of the tumor and protein expression of p53.Methods: Formalin-fixed paraffin-embedded from 52 patients with PC, at diagnosis and prior to any cancer treatment, were obtained. HPV identification was performed by nested type PCR, and miR-145 expression was obtained by qRT-PCR. Immunohistochemical analysis of p53 and Ki-67 was performed.Results: Tumoral miR-145 expression was significantly lower compared to adjacent tissue. Additionally, there was a significant reduction of miR-145 expression in invasion perineural, histological associated HPV, and absence of p53 expression in positive HPV cases. HPV infection was detected in 86.5%, the most frequent HPV16. Reduced disease-free survival was observed in patients with low expression of miR-145.Conclusions: Our data suggest that the underexpression of miR-145 may be triggered by HPV action, decreasing protein expression of p53, and being correlated with perineural invasion. Therefore, the deregulation of miR-145 provides clues as to the potential role in penile carcinogenesis and is also a potential candidate for validation in noninvasive samples.