BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands.

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

Prognostic impact of miR-125b and miR-155b and their relationship with MYC and TP53 in diffuse large B-cell lymphoma: cell-of-origin classification matters.

Tumoral microRNAs, such as miR-125b and miR-155b, are important gene expression regulators with complex pathogenetic mechanisms. However, their role in DLBCL, especially when cell-of-origin classification is considered, are still to be elucidated. In a series of 139 DLBCL cases considering germinal center (GC) versus nonGC subtypes, we investigated miR-125b and miR-155b expression by in situ hibridization and their association with some immunophenotypic presentations, including MYC, BCL2 and TP53 expression, MYC, BCL2 and BCL6 translocation status, as well as clinicopathological features and outcomes. miR-125b detection was positively correlated to the Ki-67 index (P = 0.035) in the nGC. Considering the GC subgroup, the percentage of miR-125b positive cells was also correlated to either MYC and MYC/BCL2 double expression (P = 0.047 and P = 0.049, respectively). When it comes to nGC patients, miR-155b percentage and intensity, as well as Allred score, were positively correlated to disease progression (P = 0.038, P = 0.057 and P = 0.039, respectively). In a multivariate analysis, GC phenotype was a significant independent factor associated with higher OS (P = 0.007) and, considering the nGC group, although not significant, the expression of TP53, miR-125b and miR-155b seems to be potential prognostic biomarkers in these tumors. This study demonstrated different pathways based on cell-of-origin classification and highlighted different clinical outcomes. miR-125b, miR-155b and TP53 expression may also represent potential prognostic factors in nGC-DLBCL.

High Frequency of Epstein-Barr Virus and Absence of Papillomavirus in Breast Cancer Patients from Brazilian Northeast.

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.

Evaluation of HPV and EBV in OSCC and the expression of p53, p16, E-cadherin, COX-2, MYC, and MLH1.

OBJECTIVE: This study aimed to evaluate the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and the expression of p53, p16, E-cadherin, COX-2, MLH1, and MYC in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: One hundred OSCC specimens were submitted to in situ hybridization for HPV and EBV, and immunohistochemistry for detection of the human proteins. RESULTS: Thirty-one cases showed HPV in tumor tissue. EBV was not detected in any case investigated. The HPV(+) group demonstrated an increase of staining scores for nuclear p16 (p = .047), cytoplasmic MYC (p = .002), while a decrease for nuclear MLH1 (p = .048), suggesting that HPV may upregulate the expression of the first two proteins and down-regulate the latter. CONCLUSION: Our findings reinforce the hypothesis of the HPV-related oral carcinogenesis involving the expression of p16 and MYC, and MLH1 suppression. Exclusively cytoplasmic stainings for p16, MLH1, and MYC were also associated with more advanced tumors. Finally, in view of the lack of studies correlating the HPV or EBV infection to the expression of oncoproteins, more researches assessing a broader panel of markers and employing different approaches are still necessary in order to understand the role of these viruses as well as the molecular mechanisms involved in the development and progression of oral carcinomas.

Contribution of genetic polymorphisms of interleukins IL1B-511 C/T, IL1RN VNTR, IL6-174 G/C, and IL8-251 A/T in gastric lesions: gender and Helicobacter pylori genes matter.

Stomach pathologies develop in a complex interaction between the host's genetic background and H. pylori virulent genes. Thus, our study aimed to compare active chronic gastritis (ACG), and intestinal metaplasia (IM) with inactive chronic gastritis (ICG), according to interleukin polymorphisms of IL6-174 G/C, IL8-251 A/T, IL1ß-511 C/T, and IL1RN VNTR taking into account patient gender and H. pylori genotypes. Interleukin polymorphisms were determined by RFLP-PCR and H. pylori genotype by PCR. IL6-174 GC and IL8-251 T allele showed a protective effect in women against ACG development and, conversely, IL8-251 polymorphism showed a risk for men. More virulent H. pylori strains were associated with the IL8-251 T allele and IL1ß-511 T allele in the AGC, and the vacA m1 allele and cagE gene from H. pylori was associated with the IM. Analysis of the progression of gastric lesions must take into account host variability genetic associated with genes H. pylori due to the relation between the virulent H. pylori genes and more severe gastric lesions, besides the relevance to the gender to IL6-174 and IL8-251 polymorphisms.

Detection of deletions in 1q25, 1p36 and 1pTEL and chromosome 17 aneuploidy in oral epithelial dysplasia and oral squamous cell carcinoma by fluorescence in situ hybridization (FISH).

OBJECTIVE: To identify chromosome deletions in 1q25, 1p36 and 1pTEL, and chromosome 17 ploidy status in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Samples from 57 OED and 63 OSCC were selected. FISH was performed using centromeric probes 17 and n LSIR 1p36/LSI 1q25 Dual Color Probe. RESULTS: In OED, deletions were found only in 1pTEL region (29.8%). In OSCC, there was a higher frequency of deletion in 1pTEL (79.4%), followed by 1p36 (73.0%), and 1q25 (20.6%). Advanced TNM clinical stages (III/IV) showed all the deletions studied; at early clinical stages (I/II) of OSCC, deletions were observed only in 1pTEL. The frequency of deletion in 1p36 was 17.0 times higher in OSCC at advanced clinical stages (PR: 17.00). The median number of cell nuclei with chromosome 17 aneuploidy was higher in OSCC than in OED (P < 0.001). Early clinical stages of OSCC showed lower median number nuclei with aneuploidy when compared to advanced tumors (P < 0.05). Tumors harboring deletions in 1p36, 1q25 and 1pTEL revealed higher median numbers of trisomic/polysomic nuclei when compared to lesions exhibiting no abnormalities in chromosome 1 (P < 0.05). CONCLUSION: A higher prevalence of chromosomal abnormalities was found in OSCC than in OED, while in OSCC, higher abnormalities were present in lesions with higher TNM staging. 1pTEL deletion and monosomy of chromosome 17 are possible markers for progression of OED to OSCC. 1p36 deletion and trisomy/polysomy of chromosome 17 could be markers of worse prognosis of OSCC.

Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer.

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.

EZH2 expression is dependent on MYC and TP53 regulation in diffuse large B-cell lymphoma.

EZH2 is an important epigenetic regulator, but its role in diffuse large B-cell lymphoma (DLBCL) pathogenesis and its relationship with MYC, BCL2, and TP53 expression, chromosomal rearrangements, and clinical features are still poorly understood. So, we investigated EZH2 expression and its associations with the immunophenotypic presentations, including MYC, BCL2, and TP53 expression, MYC, BCL2, and BCL6 translocation status, clinicopathological features, and therapeutic response to R-CHOP in a series of 139 DLBCL cases. EZH2 positivity was associated with MYC and TP53 expression (p = 0.0002 and p = 0.0000, respectively) and to high proliferative index (Ki67>70%, p = 0.0082). No associations were found among EZH2 expression and chromosomal translocation status. The non-germinal center (nGC) DLBCL presented most of associations observed in the general sample; however, only TP53 immunodetection showed associations with EZH2 expression in the germinal center (GC) DLBCL. EZH2 expression had no impact on therapeutic efficacy in R-CHOP-treated patients. In conclusion, EZH2 seems to be upregulated by MYC, to rely on TP53 alterations, and is associated with high proliferative tumors in DLBCL, which might be dependent on GC or nGC subclassifications. Furthermore, it is not a therapeutic efficacy marker to R-CHOP in our series.

New insights on intercontinental origins of paternal lineages in Northeast Brazil.

BACKGROUND: The current Brazilian population is the product of centuries of admixture between intercontinental founding groups. Although previous results have revealed a heterogeneous distribution of mitochondrial lineages in the Northeast region, the most targeted by foreign settlers during the sixteenth century, little is known about the paternal ancestry of this particular population. Considering historical records have documented a series of territorial invasions in the Northeast by various European populations, we aimed to characterize the male lineages found in Brazilian individuals in order to discover to what extent these migrations have influenced the present-day gene pool. Our approach consisted of employing four hierarchical multiplex assays for the investigation of 45 unique event polymorphisms in the non-recombining portion of the Y-chromosome of 280 unrelated men from several Northeast Brazilian states. RESULTS: Primary multiplex results allowed the identification of six major haplogroups, four of which were screened for downstream SNPs and enabled the observation of 19 additional lineages. Results reveal a majority of Western European haplogroups, among which R1b-S116* was the most common (63.9%), corroborating historical records of colonizations by Iberian populations. Nonetheless, FST genetic distances show similarities between Northeast Brazil and several other European populations, indicating multiple origins of settlers. Regarding Native American ancestry, our findings confirm a strong sexual bias against such haplogroups, which represented only 2.5% of individuals, highly contrasting previous results for maternal lineages. Furthermore, we document the presence of several Middle Eastern and African haplogroups, supporting a complex historical formation of this population and highlighting its uniqueness among other Brazilian regions. CONCLUSIONS: We performed a comprehensive analysis of the major Y-chromosome lineages that form the most dynamic migratory region from the Brazilian colonial period. This evidence suggests that the ongoing entry of European, Middle Eastern, and African males in the Brazilian Northeast, since at least 500 years, was significantly responsible for the present-day genetic architecture of this population.

Twist and E-cadherin deregulation might predict poor prognosis in lower lip squamous cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate the expression of Twist and E-cadherin in lower lip squamous cell carcinoma (LLSCC) and their association with clinicopathologic parameters. STUDY DESIGN: Fifty-nine cases of LLSCC were analyzed by applying immunohistochemistry techniques in a semiquantitative manner. The systems proposed by Bryne etal., Brandwein-Gensler etal., and Almangush etal. were applied for analysis of the histopathologic malignancy grading system. RESULTS: Higher E-cadherin expression (general and membrane) was observed in cases presenting with disease-free survival after 5years of follow-up (P < .05). Higher Twist expression was observed in lesions classified as being in advanced stages, displaying recurrence, and having a high degree of malignancy. A significant negative correlation was detected between cytoplasmic Twist expression and membrane E-cadherin expression (P = .028). A statistically significant relationship was detected between high total Twist expression in tumors classified as high risk by Brandwein-Gensler etal., and no significant difference was observed among total, membrane, and cytoplasmic E-cadherin expressions in LLSCC cases and the 3 applied grading systems (P > .05). CONCLUSIONS: The results of the present study suggest the potential involvement of Twist and E-cadherin in the modulation of events related to worse prognoses in LLSCC cases.

Hypermethylation of BRCA1 Gene in Meningioma in Elderly Males.

BACKGROUND/AIM: Breast cancer 1, early onset (BRCA1) gene is expressed in the cells of the breast and other tissues, where it plays a role in cell-cycle regulation, transcription, repair of DNA double-stranded breaks, ubiquitination, transcriptional regulation as well as other functions, such as cell response regulation to mitogenic signals triggered by estrogens. Considering that meningioma shows greater tumor growth during pregnancy, can express estrogen receptors and proliferate in response to estrogenic stimulation, the hypothesis that this type of tumor may share molecular mechanisms that involve exposure to estrogen should be investigated. Therefore, the aim of the present study was to investigate the BRCA1 gene methylation profile in meningioma. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (PCR) assay was performed on 50 meningioma samples from male and female patients. Statistical analysis was carried out using Fisher's exact test. RESULTS: The most important finding of this study was that 100% of the male patients over 55 years with meningioma showed BRCA1 methylated in their tumor cells. CONCLUSION: The silencing of BRCA1 through hypermethylation seems to play an important role in meningioma.

The association among HER2, MET and FOXP3 expression and tumor regression grading in gastric adenocarcinoma.

Although the introduction of the perioperative chemotherapy on the management of gastric cancer has improved patients survival, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Thus, this study evaluated the tumor regression grading (TRG) in a series of post-treatment gastric tumors and its associations with HER2, MET, and FOXP3 expression. Material of 54 gastric cancer samples was available for TRG evaluation and immunohistochemistry. We found that total and subtotal pathologic response were significantly associated to the intestinal subtype (p = 0.04) and that well-differentiated tumors were significantly correlated with total or partial response (p = 0.019). Although not associated with the TRG, FOXP3 expression in gastric tumors was associated to poorly differentiated tumors (p = 0.03), to the diffuse and mixed subtypes together (p = 0.04) and to the presence of vascular infiltration (p = 0.04), while HER2 overexpression was associated to better differentiated cases (p = 0.04) and to the absence of vascular infiltration (p = 0.02). MET expression, however, showed no association with the analyzed clinicopathological factors. This study highlights the role of tissue differentiation on pathological response to neoadjuvant chemotherapy in gastric cancer and shows no impact between FOXP3, HER2 and MET expression in terms of TRG.

Assessment of CTNNB1 gene mutations and ß-catenin immunoexpression in salivary gland pleomorphic adenomas and adenoid cystic carcinomas.

ß-Catenin exerts multiple functions in several neoplasms, playing a major role in cell signaling and tumor progression. This study analyzed possible CTNNB1 mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic carcinomas (ACCs), and determined possible differences in ß-catenin immunoexpression in relation to these mutations, as well as histopathological aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of ß-catenin distribution and cellular localization. Furthermore, ß-catenin expression was evaluated using the H-score scoring system. Mutations in CTNNB1 exon 3 were investigated by the single-strand conformational polymorphism test. Diffuse ß-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in ß-catenin cellular localization was observed between these tumors (P = 0.098). Comparisons between PA and ACC cases revealed a higher median H-score in the latter (P = 0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed in 6 PAs and 7 ACCs, with no significant difference in H-scores for ß-catenin according to mutation status (P = 0.135). ß-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence ß-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross-Reactive Nonsteroidal Anti-inflammatory Drug Hypersensitivity.

Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.

The intricate interplay between MSI and polymorphisms of DNA repair enzymes in gastric cancer H.pylori associated.

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.

mtDNA structure: the women who formed the Brazilian Northeast.

BACKGROUND: The distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization. RESULTS: Unexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups. CONCLUSIONS: Our findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.

A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil.

Background and purpose - Treatment failure of osteomyelitis can result from genetic susceptibility, highlighting polymorphisms of the interleukin-1 (IL-1) family members, central mediators of innate immunity and inflammation. Polymorphisms are DNA sequence variations that are common in the population (1% or more) and represent multiple forms of a single gene. We investigated the association of IL1RNVNTR (rs2234663) and IL1B-511C > T (rs16944) polymorphisms with osteomyelitis development in patients operated on because of bone trauma. Patients and methods - 153 patients who fulfilled the inclusion criteria were enrolled from a referral public hospital for trauma. All the patients were followed up daily until hospital discharge and, after this, on an outpatient basis. Patients were treated with prophylactic antimicrobials and surgery according to traumatology service protocol. The IL1RNVNTR and the IL1B-511C > T polymorphisms were determined by PCR and PCR-RFLP, respectively. Results - The IL1RN*2/*2 genotype was associated (OR: 7; p < 0.001) with a higher risk of osteomyelitis and was also significantly associated with Staphylococcus aureus infection. The haplotypes (combination of different markers) *2-C and *2-T were also associated with osteomyelitis development. Interpretation - IL1B-511C > T and IL1RNVNTR polymorphisms were associated with osteomyelitis development, which may have implications for patients with bone traumas. These data may be relevant for new therapeutic strategies for this disease.

Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism.

OBJECTIVE: Despite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DESIGN: Twenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E-cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. RESULTS: No significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 -160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. CONCLUSIONS: The results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands.

Association of genetic polymorphisms of IL1ß -511 C>T, IL1RN VNTR 86 bp, IL6 -174 G>C, IL10 -819 C>T and TNFα -308 G>A, involved in symptomatic patients with dengue in Brazil.

OBJECTIVE: In this study, single nucleotide polymorphisms (SNP) of interleukin (IL) 1ß -511C>T, IL1RN VNTR 86 bp, IL6 -174G>C, IL10 -819C>T and TNFα -308G>A were analyzed by PCR-RFLP with symptoms of dengue with the clinical features. SUBJECTS: 196 individuals admitted to the São José Infectious Diseases Hospital with suspected dengue infection. Dengue was confirmed in 111 of the patients. The control group consisted of 85 other individuals confirmed without dengue. RESULTS: It was demonstrated that the presence the T allele of IL1ß (P < 0.05) was associated with susceptibility to developing the disease. Other results also suggested that the polymorphism in the combinations IL6 × IL1ß (C and T alleles, respectively), IL1ß (T allele) × IL1RN (*2/*2 genotype), IL6 (C allele) × TNFα (A allele), IL10 (C/T genotype) × TNFα (A/A genotype) (P < 0.01, P = 0.01, P < 0.05 and P = 0.03, respectively) were associated with predisposition to developing the disease and its symptoms. CONCLUSIONS: In summary, the findings of this study in a Brazilian population point out the importance of studies of combinations of polymorphisms in the development of dengue, which can increase the risk of dengue infection and its severity.

Association of Polymorphisms in IL1ß -511C>T, IL1RN 86 bp VNTR, and IL6 -174G>C Genes with Clinical Dengue Signs and Symptoms in Brazilian Dengue Patients.

Dengue is an important infectious disease that has high morbidity and mortality rates in most tropical and subtropical areas of the world. The diversity of the clinical manifestations involved in the outcome of dengue virus infection is affected by the relationship between serotype/genotype of the virus, host immune status, host genetic background, and environmental factors. Polymorphisms in interleukin (IL) genes have been associated with risk of developing symptomatic dengue. This study aimed to determine the association of the single-nucleotide polymorphisms of IL1ß -511C>T, IL1RN 86 bp VNTR, and IL6 -174G>C genes with the clinical features of 198 individuals admitted to the São José Infectious Diseases Hospital with suspected dengue infection. Dengue was confirmed in 118 of the patients. The control group consisted of 80 other individuals who had symptoms similar to dengue, but negative for that. A higher frequency of increased hematocrit (p = 0.009), leukopenia (p = 0.000007), neutropenia (p = 0.0004), lymphocytosis (p = 0.00001), monocytosis (p = 0.004), atypical lymphocytes (p = 0.03), and thrombocytopenia (p = 0.0000009) was observed in the dengue patients. Among the polymorphisms studied, only IL1ß (-511C>T) was associated with dizziness, (p = 0.01), suggesting that IL1ß may be related to hypotensive episodes and increased vascular permeability. These results pointed out the importance of the IL1ß (-511C>T) polymorphism in the development of clinical symptoms of dengue symptomology.