Part 2: Deregulated Expressions of PIWI Proteins and piRNAs as New Candidate Biomarkers and Potential Therapeutic Tools in Cancer

Epigenetic abnormalities are early events in carcinogenesis and associate heterogeneity of DNA methylation, modifications of histones, and deregulation of noncoding RNAs. Aberrant expressions of PIWI proteins and piRNAs were recently observed in numerous subtypes of malignant tumors and were implicated in occurrence of most cancer hallmarks such as cell proliferation, genomic stability, apoptosis inhibition, invasion, and metastatic spread. However, this pathway is a new emerging research field, and further investigations are necessary to elucidate their oncogenic or tumor-suppressing status. Since the aberrant expression of this pathway may induce stemness, analysis of relationship between PIWI proteins, piRNAs, and cancer stem cells may open new avenues in cancer research. The objective of this review is to provide a broad overview of the emerging implication of PIWI proteins and piRNAs in carcinogenesis and their potential clinical interest as diagnostic and prognostic biomarkers and therapeutic tools

Significance of Tumor Microenvironment Scoring and Immune Biomarkers in Patient Stratification and Cancer Outcomes

Tumors appear as heterogeneous tissues that consist of tumor cells surrounding by a tumor microenvironment (TME). TME is a complex network composed of extracellular matrix (ECM), stromal cells, and immune/inflammatory cells that drive cancer cells fate from invasion to intravasation and metastasis. The stromal-inflammatory interface represents a dynamic space, in which exchange of numerous molecular information is associated with the transition into tumorigenic microenvironment. Recruitment, activation, and reprogramming of stromal and immune/inflammatory cells in the extracellular space are the consequences of a reciprocal interaction between TME and cancer cells. Recent data suggest that cancer development is influenced by TME and controlled by the host’s immune system, underlying the importance of TME components and immune biomarkers in the determination of prognosis and response to therapy. The immune classification has prognostic value and may be a useful supplement to the histopathological, molecular, and TNM classifications. Nevertheless, the complexity of quantitative immunohistochemistry and the variable assay protocols, stromal and immune cell types analyzed underscore the need to harmonize the quantified methods. It is therefore important to incorporate TME and immune scoring in determinations of cancer prognosis and to make sure they become a routine part of the histopathological diagnostic and prognostic assessment of patients

Part 1: The PIWI-piRNA Pathway Is an Immune-Like Surveillance Process That Controls Genome Integrity by Silencing Transposable Elements

PiRNAs [P-element-induced wimpy testis (PIWI)-interacting RNAs] represent the most frequent but the least well-investigated subtype of small ncRNAs and are characterized by their interaction with PIWI proteins, a subclass of the Argonaute family. PiRNAs and PIWI proteins maintain integrity of the genomic structure and regulate gene expression in germline and somatic cells. The PIWI-piRNA pathway primarily constitutes a conserved immune-like surveillance process that recognizes self and nonself. This axis controls genome integrity of germline cells and nonaging somatic cells by silencing and suppressing propagation of transposable elements through epigenetic and posttranscriptional mechanisms. However, mounting evidences indicate that the PIWI-piRNA pathway has broader implications in both germinal and somatic cells in various physiological and pathological processes. It modulates mRNAs levels of expression, stability, turnover, and translation and interacts directly with many transcription factors and signaling pathways molecules. PIWI proteins and piRNAs play pivotal roles in germline stem cell maintenance and self-renewal, fertilization and development, genes and proteins expression, genome rearrangement, and homeostasis

Cytological Spectrum of Pulmonary Histoplasmosis Diagnosed by Bronchoalveolar Lavage: 12 Years of Experience in French Guiana

Disseminated histoplasmosis is a major cause of mortality in HIV-infected patients. Rapid and efficient diagnosis of Histoplasma capsulatum is crucial. Cytopathology is available in most hospitals and represents a rapid diagnostic alternative. In this study, we reviewed 12 years of experience to describe the cytology of histoplasmosis diagnosed by bronchoalveolar lavage (BAL) in relation to patient characteristics. BAL-diagnosed pulmonary histoplasmosis concerned 17 patients (14 HIV+). BAL cellularity ranged from 76,000 to 125,000 cells/mL in HIV patients, and 117,000 to 160,000 cells/mL in non-HIV patients. Macrophages predominated in all HIV patients (from 60% to 88%), lymphocytic infiltrates ranged from 5% to 15%, and neutrophils were very heterogeneous (from 2% to 32%). The number of H. capsulatum at hot spots seemed greater in HIV-infected than in immunocompetent patients (9 to 375 vs. 4 to 10) and were inversely proportional to the CD4 counts. Yeasts were both intracellular and extracellular in 85.7% of the HIV patients. This is the most comprehensive series detailing the cytological aspects of BAL in the diagnosis of H. capsulatum, focusing on the number of yeasts and their clustering pattern. The cytological examination of the Gomori-Grocott-stained BAL allows a reliable diagnosis of histoplasmosis

SARS-CoV-2 and Mycobacterium tuberculosis coinfection: A case of unusual bronchoesophageal fistula

Tuberculosis is a treatable and curable bacterial disease caused by Mycobacterium tuberculosis that most often affects the lung. Since 2018, it has become the leading cause of death from infectious diseases. Tuberculosis is a public health problem in French Guiana. The majority of reported cases are diagnosed among people coming from neighboring Latin American countries. Since March 2020, French Guiana has been affected, like the rest of the world, by the new infectious disease COVID19 linked to the SARS-CoV-2 coronavirus. We here report a case of COVID19 and pulmonary tuberculosis coinfection. COVID19 pneumonia was the mode of discovery of the tuberculosis. In the present case, the tuberculosis appeared as parenchymal and endobronchial pseudotumoral lesion, which has been complicated by a bronchoesophageal fistula. The evolution of the parenchymal, endobronchial lesion and bronchoesophageal fistula was favorable after two months of anti-tuberculosis treatment

Long Noncoding RNAs as New Architects in Cancer Epigenetics, Prognostic Biomarkers, and Potential Therapeutic Targets

International audienc

Pathological Significance of GLUT-1 Expression in Breast Cancer Cells in Diabetic and Obese Patients: The French Guiana Study

The prevalence of obesity and type 2 diabetes is higher in French Guiana compared to mainland France. These metabolic disorders are associated with an increased risk of cancer. One of the factors involved is hyperinsulinemia that promotes the action of glucose transporter 1 (GLUT-1). The objective of this study is to characterize the expression of GLUT-1 in breast cancers cells in diabetic and obese patients compared to those who are not and to describe the clinical and histological prognostic factors of breast cancer in this population. We conducted a monocentric study including patients with breast cancer diagnosed between 2014 and 2020. Patients were classified into three groups: diabetes, obesity, and control group. The GLUT-1 expression was assessed by immunohistochemistry. In total, 199 patients were included in this study. The median age was 53.5 years, and the median tumor size was 2.8 cm. Luminal A was the most frequent molecular type (58.1%), followed by the triple-negative type (19.9%). The breast cancer in our population was characterized by a younger age at diagnosis, more aggressive molecular types, and larger tumor size. Thus, we suggest the advancement of the age of breast cancer screening in this territory. A total of 144 patients (31 diabetes, 22 obese, and 91 control group) were included for the study of GLUT-1 expression. Overexpression of GLUT-1 was observed in 60.4% of cases and in all carcinoma in situ lesions. GLUT-1 overexpression was associated with more aggressive cancers. This overexpression is correlated with high histological grade, high proliferation index, and aggressive molecular types. Our study found no difference in GLUT-1 expression between the diabetic or obese patients and the control group. These results highlight the potential role of GLUT-1 as a tumor metabolic prognostic marker and also as an interesting target therapy, independently of patient metabolic disorder

Probable anaplasmose chez un randonneur en Guyane : pourquoi il faut continuer à rechercher les maladies bactériennestransmises par les tiques

International audienceTicks are the second most common vectors of human infectious diseases worldwide, after mosquitoes. Little data is available on tick-borne diseases in French Guiana (GF), but Brazilian data describes several species of rickettsia as pathogenic. New species of Borrelia, Rickettsia and Anaplasma have recently been detected in French Guiana.Les tiques sont les deuxièmes vecteurs les plus fréquents de maladies infectieuses humaines dans le monde, après les moustiques. Peu de données sont disponibles sur les maladies transmises par les tiques en Guyane (GF), mais les données brésiliennes décrivent plusieurs espèces de rickettsies comme pathogènes. De nouvelles espèces de Borrelia, Rickettsia et Anaplasma ont récemment été détectées en Guyane Française

E6/E7 Sequence Diversity of High-Risk Human Papillomaviruses in Two Geographically Isolated Populations of French Guiana

International audienceAmerindian and Maroon populations of French Guiana have been living in isolation for generations and sexual networks remained mostly endogamous. The present study aimed to describe the phylogeny of E6 and E7 sequences of the most common high-risk HPV genotypes in these regions, to ascertain the diversity of intra-type variants and describe evolutionary relationships. There were 106 women with at least one of HPV16, 18, 31, 52, 58, and 68 genotypes. The most clear-cut phylogenetic pattern was obtained for HPV18 and HPV58 for which the major branches were crisply divided between Amerindian villages on the Oyapock and Maroon villages on the Maroni. Such clustering was less clear for HPV31 and 52. For HPV16, there was also some evidence of clustering on the Oyapock with type A European viruses and on the Maroni with type B and C African viruses among Maroon women. HPV68 showed the largest sequence heterogeneity of the six genotypes at both nucleotide and amino acid levels and was restricted to Maroon women. The present results show that there were significant geographically based differences of E6 and E7 oncogenes. These differences were compatible with different ancestral virus populations and local virus evolution in a context of prolonged population isolation