RESUMO
OBJECTIVE: This study aimed to determine the presence of Epstein-Barr Virus (EBV) and Human papillomavirus (HPV) in breast cancer with patients from Northeast of Brazil, considering the molecular subtypes and also taking in account the relation with TP53 immunoexpression. METHODS: Seventy-five samples of invasive breast carcinoma with no special type were selected from pathology archives at Federal University of Ceará. EBV was detected by In situ hybridization (ISH) and immunohistochemistry (IHC) and HPV was detected by PCR. ISH was performed using EBER1 probe (Shibata et al., 1991; Bacchi et al., 1996) while IHC was performed on histological formalin-fixed paraffin-embedded tissue samples (Hsu et al., 1981). PCR methodology (Haws et al., 2004) was used to amplify the genetic material of human papillomavirus. The amplification products were electrophoretic analyzed on 1% agarose gel. The data analyses were carried out using the statistical software EPINFO® version 6.04d and SPSS version 17.0 (SPSS Inc., Chicago, IL). Statistically significant differences were evaluated by the chi-square test and Fisher's exact test and correlations between groups were analyzed by Spearman's and Pearson's rank correlation coefficient. RESULTS: 69.4% of the cases were EBNA1 positives by IHC. EBNA1 positive tumors had lower Ki-67 index (0-40%), while EBNA1 negative cases had relevant higher Ki-67 index (41-100%) (p = 0.06). EBV was present in all tumor grades, with a high frequency in grade I and III tumors comparing to EBNA1 negative cases. No HPV positive cases were observed. CONCLUSION: Regarding the results from this study, we support the hypothesis that EBV can be involved on breast tumorigenesis.
Assuntos
Neoplasias da Mama , Infecções por Vírus Epstein-Barr , Brasil/epidemiologia , Neoplasias da Mama/patologia , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Antígeno Ki-67 , Papillomaviridae/genéticaRESUMO
Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR. MSI was observed in 47.5% of the cases and it was associated with the ERCC1 polymorphic allele, whereas MSI-H was associated with the XRCC3 heterozygous genotype. MSI was more frequent in intestinal gastric cancer (IGC), where it was associated with ERCC1 or RAD51 polymorphic alleles. Also, MSI-H was associated with the XRCC3 heterozygous. In diffuse gastric cancer (DGC), almost all of MGMT polymorphic genotype carriers showed MSI. Helicobacter pylori was positive in 94% of the cases and the most virulent strains were associated with MSI, mainly MSI-H. When the subtypes were considered, these associations were found only in the IGC and associated with more virulent strains. Among the cases with microsatellite instability, IGC showed a correlation between the XPD wild-type and the ERCC1 polymorphic allele, and all of them were infected by the most virulent strains. On the other hand, in DGC, the XPD polymorphic allele was correlated with the XRCC3 wild-type with no prevalence of H.pylori virulence. Our data demonstrated that polymorphisms in repair enzymes can interfere with the efficiency of the repair process, but it differs depending on the histological subtype and H.pylori involvement. Besides nucleotide excision repair, base excision repair and mismatch repair pathway, the homologous recombination are also involved.
Assuntos
Adenocarcinoma/genética , Enzimas Reparadoras do DNA/genética , Infecções por Helicobacter/genética , Instabilidade de Microssatélites , Neoplasias Gástricas/genética , Adenocarcinoma/microbiologia , Sequência de Bases , Reparo do DNA , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/microbiologiaRESUMO
Background: Although the canine visceral leishmaniasis be characterized as a severe systemic disease, few studies have been conducted describing the main histopathological alterations found in the various organs of the host affected by the parasite. This paper evaluated the structural and immune-inflammatory changes of the spleen, liver, popliteal lymph nodes (PLN) and skin of naturally infected dogs in different clinical forms of canine visceral leishmaniasis. Material, Methods & Results: Forty seven adult dogs were used, varying in age and weight, selected by Immunofluorescence Assay (IFA), were considered positive IFA titres of ≥ 1:40 and the parasitological examination of L. infantum amastigotes forms in bone marrow smears. The dogs were grouped according to the clinical signs associated to the disease: negative dogs (ND = 7), subclinical dogs (SD = 20) and clinical dogs (CD = 20). After the euthanasia procedure, all animals were weighed, and then the spleen and liver were dissected for relative weights measurements. Fragments of spleen, liver, PLN and skin were collected and subjected to procedures for histology (H&E). The same samples were subjected to immunohistochemical analysis for detection of L. infantum amastigotes. The authors observed increased relative weight of spleen and liver of the CD and SD groups (P < 0.05). Discrete hypoplasia of red and white pulps and capsular thickening, moderate hypertrophy of red and white pulps and intense splenic congestion were observed in the spleen in group SD, whereas a slight thickening of the capsule and hypertrophy of red and white pulps, intense congestion and moderate subcapsular fibrosis and hypoplasia of the splenic red and white pulps were found in the CD group. Histological evaluation of the liver showed moderate periportal inflammatory infiltrate, hypertrophy/hyperplasia of Kupffer cells and congestion, slight thickening of the capsule and intralobular granulomas in the SD group, while moderate peri-portal inflammatory infiltrate, hypertrophy/hyperplasia of Kupffer cells, congestion, thickening of the capsule and intralobular granulomas were found in the CD group. The PLN histologic evaluation presented discrete capsular inflammation, congestion, hemosiderosis and hypertrophy/hyperplasia of lymphatic nodules and moderate hypertrophy/hyperplasia of cortical and medullar in the SD group, while slight capsular inflammation, congestion, hemosiderosis and hypertrophy/hyperplasia of lymphatic nodules and moderate hypertrophy/hyperplasia of cortical and medullar were found in the CD group. The main change observed in the skin was moderate histiolymphocyte inflammatory infiltrate in the SD group. The greatest parasite density of L. infantum amastigotes could be observed in the spleen. Discussion: The capsular thickening, subcapsular fi brosis and hypoplastic spleen can be explained by the disease chronicity. The liver infection caused by L. infantum has the ability to self-resolute through an immune response mediated by Th1 lymphocytes, mono-nuclear cells and involving the Kupffer cells, macrophages and subsequent granuloma formation. The hypertrophy/hyperplasia of cortical and medullary in lymph nodes is considered the most relevant change, because they suggest that the immunopathological status is a characteristic of chronic infection. In dogs infected by L. infantum, the ears are the skin areas where the lesions and inflammatory infiltrates are most evident. This unequal tropism doesn't occurs solely because of the area being the preferred location by transmitting insects, but also by the high incidence of lesions caused by ectoparasites and itchy reactions. It follows that organs and tissues of dogs naturally infected by L. infantum have histological changes consistent with immune-inflammatory response, demonstrating the functional impairment of the same.