EZH2 expression is associated with inferior overall survival in mantle cell lymphoma.

Enhancer of zeste homolog 2 (EZH2) is a catalytic component of the polycomb repressive complex 2 (PRC2) which reduces gene expression via trimethylation of a lysine residue of histone 3 (H3K27me3). Expression of EZH2 has not been assessed systematically in mantle cell lymphoma (MCL). Expression of EZH2 was assessed by immunohistochemistry in 166 patients with MCL. We also assessed other PRC2 components and H3K27me3. Fifty-seven (38%) of MCL patients were positive for EZH2 using 40% cutoff. EZH2 expression was associated with aggressive histologic variants (65% vs. 29%, p < 0.001), high Ki-67 proliferation rate (median, 72% vs. 19%, p < 0.001), and p53 overexpression (43% vs. 2%, p < 0.001). EZH2 expression did not correlate with expression of other PRC2 components (EED and SUZ12), H3K27me3, MHC-I, and MHC-II. Patients with EZH2 expression (EZH2+) had a poorer overall survival (OS) compared with patients without EZH2 expression (EZH2-) (median OS: 3.9 years versus 9.4 years, respectively, p < 0.001). EZH2 expression also predicted a poorer prognosis in MCL patients with classic histology (median OS, 4.6 years for EZH2+ and 9.6 years for EZH2-negative, respectively, p < 0.001) as well as aggressive histology (median OS, 3.7 years for EZH2+ and 7.9 years for EZH2-negative, respectively, p = 0.046). However, EZH2 expression did not independently correlate with overall survival in a multivariate analysis. Gene expression analysis and pathway enrichment analysis demonstrated a significant enrichment in cell cycle and mitotic transition pathways in MCL with EZH2 expression. EZH2 expression detected by immunohistochemistry is present in 38% of MCL cases and it is associated with high proliferation rate, p53 overexpression, aggressive histologic variants, and poorer OS. Based on gene expression profiling data, EZH2 expression could potentiate cell cycle machinery in MCL. These data suggest that assessment of EZH2 expression could be useful to stratify MCL patients into low- and high-risk groups.

Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens.

Antimicrobial peptides (AMPs) are gaining interest as potential therapeutic agents. Peptides derived from bovine lactoferricin B (LfcinB) have been reported to exhibit antimicrobial activity, and the LfcinB RRWQWR sequence is the smallest known motif that exhibits antibacterial and cytotoxic activity. Our goal was to examine the effect of multicopy arrangements of the RRWQWR motif, on its antibacterial activity against healthcare-associated infections (HCAIs). Linear and branched peptides containing the RRWQWR motif were generated using solid phase peptide synthesis-Fmoc/tBu methodology, purified, and characterized using reverse phase-high performance liquid chromatography and matrix-assisted laser desorption/ionization time of flight mass spectrometry. For each peptide, the antibacterial activity against Staphylococcus aureus (ATCC 25923 and 33591 strains) and Klebsiella pneumoniae (ATCC 13883 and 700603 strains) was assessed by measuring the minimum inhibitory and the minimum bactericidal concentrations, in the exponential phase. Cells were observed by scanning electron microscopy, and the hemolytic activity of the peptides was assessed. The overall results demonstrate that, compared to linear analogues, polyvalent presentation of the RRWQWR motif enhances its antibacterial activity against both Gram-negative and Gram-positive bacteria even on resistant strain.

Linfoma T intestinal monomórfico CD56+. Primer caso informado en Colombia y revisión de la literatura / Monomorphic Intestinal T-Cell Lymphoma. First reported case in Colombia and review of the literature

Se informa el caso de una mujer de 80 años con hallazgo incidental de masa abdominal en mesogastrio. Se le realiza resección de intestino delgado por sospecha de absceso con síndrome adherencial. El estudio patológico de la pieza quirúrgica demostró compromiso por linfoma no Hodgkin T monomórfico CD56+. Los linfomas T del tubo digestivo son inusuales; corresponden al 5% de las neoplasias linfoides de esta localización. El linfoma intestinal T monomórfico CD56+ corresponde a 10-20% de los linfomas T intestinales. Se presenta en regiones donde la enfermedad celiaca es infrecuente y no se asocia a enteropatía. Su curso es agresivo y habitualmente se manifiesta como una emergencia quirúrgica por obstrucción o perforación intestinal.

80 year old woman with incidental finding of abdominal mass in midgut, in which small bowel resection is performed for suspected abscess associated to surgical adhesions. Pathological examination of the surgical specimen showed a monomorphic CD56+ T cell lymphoma. T-cell lymphomas of the digestive tract are rare, accounting for 5% of all lymphoid neoplasms in this location. Monomorphic CD56+ intestinal T cell lymphoma corresponds to 10 - 20% of T cell intestinal lymphomas. This tumor occurs in regions where celiac disease is rare and it is not associated with enteropathy. Its course is aggressive and usually manifests as a surgical emergency by intestinal obstruction or perforation.

La biopsia hepática en niños, experiencia de 5 años en un hospital pediátrico colombiano / Liver Biopsy in Children Under 5 Years Experience in a Colombian Pediatric Hospital

Objetivo: evaluar la distribución por frecuencia de las enfermedades hepáticas que justificaron el estudio por biopsia en pacientes pediátricos colombianos. Metodología: se evaluaron las biopsias de hígado realizadas durante 5 años en un hospital pediátrico y se agruparon las enfermedades hepáticas por diagnóstico y edad. Resultados: se encontraron 182 estudios histopatológicos de 168 pacientes, 14 de ellos contaban con 2 procedimientos; 53,6% fueron niños y 46,4%, niñas. El grupo de edad con más biopsias fue el de los lactantes menores y la colestasis fue en ellos la indicación más frecuente del estudio. Los grupos de enfermedades más diagnosticadas fueron los procesos inflamatorios (30,2%), las anormalidades de la vía biliar (26,4%), las enfermedades tumorales (14,9%) y los trastornos metabólicos/de depósito (9,3%). Los porcentajes restantes correspondieron a entidades infrecuentes y biopsias normales. Conclusión: la biopsia hepática es una herramienta útil y práctica en el diagnóstico de la enfermedad hepática pediátrica cuando se combina con datos clínicos y de laboratorio. En nuestro estudio, los procesos inflamatorios, las anormalidades de la vía biliar y las enfermedades tumorales fueron las categorías más diagnosticadas.

Objective: The objective of this study was to evaluate the frequency and distribution of liver diseases justifying liver biopsies in Colombian pediatric patients. Methodology: Liver biopsies performed at a pediatric hospital over a period of 5 years were assessed and then sorted according to age groups and diagnoses. Results: A total of 182 histopathological studies of 168 patients (14 of whom had two procedures each.) were found: 53.6% were boys, and 46.4% were girls. Young infants were the age group which had the most biopsies, and cholestasis was the most frequent reason for these biopsies. Other diseases diagnosed included inflammatory processes (30.2%), abnormalities of the biliary tract (26.4%), tumor diseases (14.9%) and metabolic/storage disorders (9.3%). The remaining percentages were for rare entities and normal biopsies. Conclusion: Liver biopsies are useful and practical for the diagnosis of pediatric liver disease when combined with clinical and laboratory data. In our study, inflammatory processes, abnormalities of the biliary tract and tumor diseases were the most frequently diagnosed categories.

Gastropatía reactiva: Frecuencia en biopsias endoscópicas evaluadas en la Universidad Nacional de Colombia / Reactive gastropathy: Frequency in endoscopic biopsies evaluated at the Universidad Nacional de Colombia

La gastropatía reactiva (GR) es producida principalmente por antiinflamatorios no esteroideos (AINEs) y reflujo biliar; puede presentarse aisladamente o coexistir con otros tipos de gastritis crónica (GC). Se revisaron 5.079 informes de estudios histopatológicos de biopsias gástricas de 4.254 pacientes, 825 en seguimiento con 2 a 7 estudios. La GR correspondió a 12,8% de los diagnósticos, las GC no atrófica (GCNA) y atrófica multifocal (GCAMF) correspondieron a 63,4% y 27,3% respectivamente. La infección por Helicobacter pylori se presentó en 61,6% de casos con GCNA, 51,5% con GCAMF, 18,5% con GR (p < 0.0001); en casos con coexistencia de GR+GCNA fue 43,9% y de 40,7% para GCAMF+GR. En pacientes en seguimiento aumentaron los diagnósticos de GR: 2 estudios con 22,2%, 3 estudios con 26,7% y 4-7 estudios con 28,8%; los hallazgos histológicos de GR en estos casos posiblemente son residuales, luego de la desaparición de los infiltrados inflamatorios por el tratamiento.

Reactive gastropathy (RG) is primarily produced by non-steroid antiinflammatory drugs (NSAIDs) and bile reflux. It can occur alone or coexist with other types of chronic gastritis (CG). 5,079 histopathological reports of gastric biopsies from 4,254 patients were reviewed: 825 of them had 2 to 7 follow-up studies. 12.8% of these patients were diagnosed with GR while 63.4% were diagnosed with chronic non-atrophic gastritis (CNAG) and 27.3% were diagnosed with chronic multifocal atrophic gastritis (CMAG). Helicobacter pylori infections were found in 61.6% of the cases with CNAG, 51.5% with CMAG, and in 18.5% of cases with GR only (p <0.0001). Among patients suffering from both RG and CNAG 43.9% had H. pylori infections. 40.7% of those suffering from both CMAG and RG were infected with H. pylori. During monitoring of patients RG diagnoses increased to 22.2% in the second study, 26.7% in the third study, and 28.8% in the fourth through seventh studies. Histological findings of RG in these cases are probably residual following disappearance of inflammatory infiltrates due to treatment.