Anticorpos anti-trypanosoma cruzi como preditivos de infecção por leishmania infantum

Leishmania infantum and Trypanosoma cruzi are trypanosomatids of medical importance and are, respectively, the etiologic agents of visceral leishmaniasis (VL) and Chagas disease (CD) in Brazil. People infected with L. infantum or T. cruzi may develop asymptomatically, enabling the transmission of pathogens through blood transfusion and / or organs. The assessment of the infection by T. cruzi is included among the tests performed for screening blood donors in Brazil, however, there is no availability of tests for Leishmania. Serological tests for T. cruzi are very sensitive, but not specific, and may have cross-reactions with other microorganisms. Thus, the aim of this study was to determine the prevalence of Leishmania infection in blood donors and assess whether the serological test for T. cruzi detect L. infantum. Among the 300 blood samples from donors, discarded in 2011, 61 were T. cruzi positive, 203 were from donors with other infections and 36 were from handbags with low blood volume, but without infection. We also assessed 144 samples from donors without infections and able to donate blood, totaling 444 subjects. DNA was extracted from blood samples of all to perform quantitative PCR (qPCR) to detect Leishmania DNA. The buffy coat obtained from all samples was grown in Schneider medium supplemented and NNN. All samples were evaluated for the presence of anti-Leishmania antibody. The serological results indicate a percentage of 22% of Leishmania infection in blood samples obtained from discarded bags. A total of 60% of samples positive in ELISA for T. cruzi were negative by IFI, used as confirmatory test, ie 60% false positive for Chagas. Among these samples false positive for Chagas, 72% were positive by ELISA for Leishmania characterizing the occurrence of cross reaction between serologic assays. Of the 300 cultures performed, 18 grew parasites that were typed by qPCR and specific isoenzymes, found the species Leishmania infantum crops. Among the 18 cultures, 4 were purged from scholarships for low volume and all negative serology blood bank, thus demonstrating that there is a real risk of Leishmania transmission via transfusion. It is concluded that in an area endemic for leishmaniasis in Brazil, serological diagnosis performed to detect infection by T. cruzi among blood donors can identify infection by L. infantum and although cause false positive for Chagas, this cross-reactivity reduces the risk of Leishmania infection via blood transfusion, since tests are not applied specific detection of the parasite. In this way, there remains the need to discuss the implementation of a specific serological screening test for Leishmania in endemic countries such as Brazil

Anticorpos anti-trypanosoma cruzi como preditivos de infecção por leishmania infantum

Leishmania infantum and Trypanosoma cruzi are trypanosomatids of medical importance and are, respectively, the etiologic agents of visceral leishmaniasis (VL) and Chagas disease (CD) in Brazil. People infected with L. infantum or T. cruzi may develop asymptomatically, enabling the transmission of pathogens through blood transfusion and / or organs. The assessment of the infection by T. cruzi is included among the tests performed for screening blood donors in Brazil, however, there is no availability of tests for Leishmania. Serological tests for T. cruzi are very sensitive, but not specific, and may have cross-reactions with other microorganisms. Thus, the aim of this study was to determine the prevalence of Leishmania infection in blood donors and assess whether the serological test for T. cruzi detect L. infantum. Among the 300 blood samples from donors, discarded in 2011, 61 were T. cruzi positive, 203 were from donors with other infections and 36 were from handbags with low blood volume, but without infection. We also assessed 144 samples from donors without infections and able to donate blood, totaling 444 subjects. DNA was extracted from blood samples of all to perform quantitative PCR (qPCR) to detect Leishmania DNA. The buffy coat obtained from all samples was grown in Schneider medium supplemented and NNN. All samples were evaluated for the presence of anti-Leishmania antibody. The serological results indicate a percentage of 22% of Leishmania infection in blood samples obtained from discarded bags. A total of 60% of samples positive in ELISA for T. cruzi were negative by IFI, used as confirmatory test, ie 60% false positive for Chagas. Among these samples false positive for Chagas, 72% were positive by ELISA for Leishmania characterizing the occurrence of cross reaction between serologic assays. Of the 300 cultures performed, 18 grew parasites that were typed by qPCR and specific isoenzymes, found the species Leishmania infantum crops. Among the 18 cultures, 4 were purged from scholarships for low volume and all negative serology blood bank, thus demonstrating that there is a real risk of Leishmania transmission via transfusion. It is concluded that in an area endemic for leishmaniasis in Brazil, serological diagnosis performed to detect infection by T. cruzi among blood donors can identify infection by L. infantum and although cause false positive for Chagas, this cross-reactivity reduces the risk of Leishmania infection via blood transfusion, since tests are not applied specific detection of the parasite. In this way, there remains the need to discuss the implementation of a specific serological screening test for Leishmania in endemic countries such as Brazil

Prevalência e fatores associados à testagem para HIV em homens que fazem sexo com homens

A infecção por HIV/Aids (vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida) constitui um importante problema mundial de Saúde Pública. Dados do último boletim apresentado pela UNAIDS (Organização das Nações Unidas para Aids) em 2013, apontam que mais de 35 milhões de pessoas vivem com HIV em todo mundo. No Brasil, a epidemia é concentrada, com prevalência de infecção menor que 1% na população de 15 a 49 anos, porém chegando a 10,5% entre homens que fazem sexo com homens (HSH). O diagnóstico precoce do HIV se associa a uma redução da morbidade, mortalidade e também da transmissão desta infecção. O presente estudo tem o objetivo de avaliar a prevalência e fatores associados à testagem prévia para HIV na população de HSH dos municípios de Natal/RN e Parnamirim/RN. Os participantes respondiam a um questionário contendo perguntas referentes a dados sociodemográficos, padrões de relacionamento sexual, conhecimentos sobre HIV/Aids, uso de preservativo, consumo de álcool, drogas e busca de testagem para HIV e sífilis. Em seguida, os que desejassem poderiam realizar teste rápido para HIV e sífilis. No total, foram pesquisados 101 sujeitos, destes, 70 foram recrutados com a utilização da técnica Respondent Driving Sample, e 31 com uma amostra de conveniência. O teste de HIV havia sido realizado por 63,3% dos homens pelo menos uma vez na vida. A testagem prévia para HIV foi associada à idade (27 anos ou mais), realização prévia do teste para sífilis, conhecimento sobre locais onde o teste de HIV é feito gratuitamente e resultado positivo para sífilis no momento da pesquisa. A prevalência de testagem para HIV na amostra foi baixa, semelhante ao verificado em outros estudos com a população HSH. Ações que priorizem a divulgação de locais onde o anti-HIV pode ser realizado gratuitamente e direcionadas para o público jovem parecem ser as mais adequadas para a ampliação da testagem entre os HSH na nossa realidade

Estado nutricional e efeito da vitamina A na resposta imune frente à infecção por Leishmania Infantum

Nutritional status is an important determinant to the response against Leishmania infection, although few studies have characterized the molecular basis for the association found between malnutrition and the disease. Vitamin A supplementation has long been used in developing countries to prevent mortality by diarrheal and respiratory diseases, but there are no studies on the role of vitamin A in Leishmania infection, although we and others have found vitamin A deficiency in visceral Leishmaniasis (VL). Regulatory T cells are induced in vitro by vitamin A metabolites and are considered important cells implicated T CD4+ cell suppression in human VL. This work aimed to examine the correlation of nutritional status and the effect of vitamin A in the response against Leishmania infantum infection. A total of 179 children were studied: 31 had active VL, 33 VL history, 44 were DTH+ and 71 were DTH- and had negative antibody to Leishmania (DTH-/Ac-). Peripheral blood monuclear cells were isolated in a subgroup of 10 active VL and 16 DTH-/Ac- children and cultivated for 20h under 5 different conditions: 1) Medium, 2) Soluble promastigote L. infantum antigens (SLA), 3) All-trans retinoic acid (ATRA), 4) SLA + ATRA and 5) Concanavalin A. T CD4+CD25highFoxp3+, T CD4+CD25-Foxp3- and CD14+ monocytes were stained and studied by flow cytometry for IL-10, TGF-β and IL-17 production. Nutritional status was compromised in VL children, which presented lower BMI/Age and retinol concentrations when compared to healthy controls. We found a negative correlation between nutritional status (measured by BMI/Age and serum retinol) and anti-Leishmania antibodies and acute phase proteins. There was no correlation between nutritional status and parasite load. ATRA presented a dual effect in Treg cells and monocytes: In healthy children (DTH-/Ac-), it induced a regulatory response, increasing IL-10 and TGF-β production; in VL children it modulated the immune response, preventing increased IL-10 production after SLA stimulation. Furthermore, we found a positive correlation between BMI/Age and IL-17 production and negative correlation between serum retinol and IL-10 and TGF-β production in T CD4+CD25highFoxp3+ cells after SLA stimulus. Our results show a potential dual role of vitamin A in the immune system: improvement of regulatory profile during homeostasis and down modulation of IL-10 in Treg cells and monocytes during symptomatic VL. Therefore, the use of vitamin A concomitant to VL therapy might improve recovery from disease status in Leishmania infantum infection

Ocorrência da infecção por Toxoplasma gondii e avaliação da imunização em caprinos do sertão do cabugi, Rio Grande do Norte

Toxoplasmosis is one zoonosis caused by Toxoplasma gondii protozoan. Goats, amongst the production animals, are one of the species most susceptible to this parasite, being one them main involved agents in ovine and goat abortions, determining great economic losses and implications for public health, since the presence it parasite in the products of goat origin, consist in one of the main sources of infection for the man. In this study 244 blood samples in 8 farms situated in 4 cities from the Sertão do Cabugi region, Rio Grande do Norte State, northeast of Brazil and, tested by ELISA assay. The results had shown a prevalence of 47.13% for anti- T. gondii antibodies and a significant association between positivity and variable evaluated as age, locality and property. The IgG avidity assay evaluated in 115 positive samples was carried to discriminate acute and chronic infection. Twelve samples (10.4%) had presented antibodies of low avidity while 103 (89.6%) presented high avidity antibodies; indicating that most of the animals was precocious exposure to the parasite. Significant difference was verified only for the variable sex. We also evaluate the capacity of recombinant adenoviruses codifying SAG1, SAG2, SAG3 and CMV in inducing activation of specific immune response in goat. These 109 animals received 109 pfu of the AdSAG1, AdSAG2, AdSAG3, AdCMV or PBS in vaccine protocol with 3 immunizations. Serum samples of the each animal, before and after mmunization, had been submitted to the ELISA. The results demonstrate that the immunizations had induced the production of IgG antibodies specific against T. gondii proteins

Frequência da infecção por Toxoplasma gondii em galinhas caipira e frangos de corte em regiões dos Estados do Rio Grande do Norte e Paraíba

Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, a protozoan that has a cosmopolitan geographic distribution and low host specificity. Usually a benign and selflimiting, infection can manifest itself in a severe systemic becoming overwhelming in fetuses and patients with immunosuppression. Domestic fowl are considered one of the most important hosts in the epidemiology of toxoplasmosis, since they are potential sources of infection for humans, in addition to playing the role of important indicators of environmental contamination by oocysts of T. gondii. We studied the prevalence of infection by the protozoan in chickens of different breeding systems mesoregions from the states of Rio Grande do Norte and Paraiba: broilers from commercial farms (200/PB) and free-range chickens of small farms (322/RN and PB). Were standardized IFAT and ELISA techniques for detecting specific antibodies in blood samples of birds, and commercial kit was used to determine the prevalence by IHAT. There was no seropositive reaction by T. gondii in the samples of broilers tested, indicating that the particularities of intensive management limit the chances of infection for these animals. Among the hens, the frequency of IgG anti-T. gondii diagnosed by the techniques of IHAT, IFAT and ELISA, respectively, were 3.73% (12/322), 37.88% (122/322) and 40.37% (130/322), for both young and adult animals. Amongst the seropositive samples by IFAT, 33 (27.05%) were positive at a dilution of 1:16, in 1:32, 31 (25.41%), in 1:64, 24 (19.67%), 15 (12.29%) in 1:128, and 19 presented titer greater than or equal to 1:256 (15.57%). The evaluation of the presence of anti-T. gondii should be careful, and reagents IHAT provided erratic results in this measure for the specie studied. This suggests the need for own standardization of the kit before the use in epidemiological studies in animal species. On the other hand, substantial agreement observed between IFAT and ELISA techniques (Kappa = 0.62) enables these methods as effective methodologies for the diagnosis of toxoplasmosis in chickens. The high prevalence of specific antibodies among poultry in the region studied attempts to the potential risk of transmission of toxoplasmosis to humans

Soroepidemiologia da infecção pelo Trypanosoma cruzi na zona rural do semiárido do estado do Rio Grande do Norte, Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Perfil de imunoglobulinas e correlação de autoanticorpos com a ocorrência de diversas formas clínicas em pacientes chagásicos crônicos

Introdução: O dano miocárdico na doença de Chagas resulta tanto da ação parasitária quanto da resposta imune do hospedeiro humano. O mimetismo molecular entre proteínas do Trypanosoma cruzi e vários antígenos do hospedeiro tem sido amplamente descrito gerando células T CD8+ e anticorpos autorreativos. Entretanto, a geração dos autoanticorpos e seu papel na imunopatogenia da doença de Chagas ainda não têm sido elucidados, o que nos levou, neste trabalho, a avaliar a produção de imunoglobulina G total (IgGt) e seus isotipos anti-T. cruzi, proteínas cardíacas e sua possível associação com as diferentes formas clínicas da doença de Chagas. Métodos: A produção de IgGt e isotipos foi mensurada pelo método de ELISA no soro de pacientes com as formas clínicas indeterminada (IND, n=72), cardíaca (CARD, n=47) e digestiva/cardio-digestiva (DIG/CARD-DIG, n=12) da doença de Chagas, usando como antígenos as formas epimastigota e tripomastigota do T. cruzi e proteínas cardíacas humana (miosina e troponina T). As amostras de indivíduos não infectados saudáveis (CONT, n= 30) e pacientes com cardiomiopatia isquêmica (ISCH, n=15) foram usadas como controle. Os títulos de autoanticorpos foram correlacionados com parâmetros da função cardíaca obtidos por exames eletrocardiográficos, radiográficos e ecocardiográficos. Resultados: Neste estudo foram incluídos 131 indivíduos sem diferença significativa relativa à idade ou sexo. Destes, 55% foram classificados como IND, 35,9% CARD e 9,1% DIG/CARD-DIG. Os títulos de IgGt foram mais elevados em pacientes com as formas clínicas IND, CARD e DIG/CARD-DIG do que em indivíduos CONT e ISCH usando os antígenos as formas tripomastigotas e epimastigotas do T. cruzi e, proteínas cardíacas humanas. Os pacientes com formas clínicas CARD e DIG/CARD-DIG mostraram a produção mais elevada de IgG total dirigida contra antígenos de tripomastigota e epimastigota do que os IND. Os grupos de pacientes IND e CARD apresentaram uma similar produção de IgG total específica direcionada à miosina e troponina T, e mais elevada do que em indivíduos CONT e ISCH. Há uma correlação negativa entre a produção de anticorpos anti-proteínas cardíacas com a fração de ejeção do ventrículo esquerdo (FEVE) em pacientes chagásicos crônicos. Os pacientes foram agrupados em baixo e alto produtores de autoanticorpos e comparados com a fração de ejeção demonstrando que em pacientes alto produtores de anti-troponina T (p=0.042) e miosina (p=0.013) a FEVE foi mais baixa do que os baixo produtores. A maioria dos pacientes chagásicos produz simultaneamente autoanticorpos direcionados à ambas proteínas cardíacas (r=0.9508, p=0.0001). Conclusões: Estes resultados indicam que os autoanticorpos anti- troponina T e miosina cardíaca parecem induzir redução FEVE e deve ser associado com o desenvolvimento de cardiomiopatia chagásica

Expressão imuno-histoquímica dos marcadores angiogênicos CD105 (endoglina) e CD34 em hemangiomas e granulomas piogênicos orais

Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed

Expressão imuno-histoquímica do cd8, foxp3, Tgf β, tnf α e nf-кb em displasias epiteliais e Carcinomas epidermóides orais

The Oral Epithelial Dysplasia (OED) is the lesion that precedes or co-exists with the Oral Squamous Cell Carcinoma (OSCC), presenting molecular and/or histological similar alterations. The divergences about the malignization potential of OEDs and the role of inflammation in this process make hard the early diagnosis and evaluation of OSCCs aggressiveness. Thus, it became the goal of this study to evaluate the role of inflammation in oral carcinogenesis and tumoral aggressiveness. For this purpose a morphological study was performed in 20 OED cases and 40 OSCC cases to detect the malignization potential of OEDs and the histologic malignancy grading (HMG) of OSCCs, analyzing superficial masses for dismorphism evaluation and the invasive front for evaluation of tumoral growing; and immunohistochemical, using anti-CD8, anti-FOXP3, anti-TGFβ, anti-TNFα and anti-NF-кB antibodies, comparing their with the types lesion, histological degree and intensity of the inflammatory infiltrate. The results were statistically significant for the parameters: cell maturity (p=0,0001), masses presence (p=0,038) and dismorphism (p=0,037), when associated to HMG. To compare the expression of the markers with the types lesion, a significantly higher expression of CD8 (p=0,001) and NF-кB (p=0,002) in the OED, and also a smaller expression of the epithelial TGFβ in the severe OEDs (p=0,011), without significant expression between OSCC degrees. By relating the expression of the studied markers with the inflammatory infiltrate intensity, a positive relation was observed with: inflammatory TNFα(p=0,003), epithelial TNFα and NF-кB (p=0,051 and p=0,004), in OEDs; and with CD8 (p=0,021) and TNFα (p=0,015) in conjunctive OSCCs; and a negative relation with epithelial TNFα (p=0,034) in OSCCs. No significant relation was found between FOXP3 with any of the studied variables. These findings lead to the conclusion that, the study of the invasive front is as important as the study of superficial masses for the evaluation of tumoral aggressiveness; the intensity of the inflammatory infiltrate has no use as a parameter for prognostic evaluation of OSCC in routine exams, but, the molecular events detected in this study may be necessary to give basis for determining the malignant potential in OEDs and aggressiveness in OSCCs

Exprassão imuno-histoquímica dos fatores de reabsorção óssea em lesões centrais e periféricas de células gigantes

The Giant Cell Lesions, both the Central Giant Cells Lesions (CGCL) as the Peripheral Giant Cells Lesions (PGCL), correspond to a group of oral lesions that are histologically similar entities; however they show a variable clinical behaviour. The purpose of this study was to compare the immunohistochemical expression of bone resorption factors RANK (Receptor Activator of Nuclear Factor kappa B), RANKL (Receptor Activator of Nuclear Factor kappa B Ligand) and OPG (Osteoprotegerin) between CGCL and PGCL. Additionally, these bone resorption factors were examined in terms of aggressiveness of these lesions. The sample consisted of 61 cases, 30 cases of PGCL and 31 CGCL (16 non-aggressive and 15 aggressive). The analysis was performed by quantification of mononuclear cells (MO) and giant multinucleated cells (CG) immunopositive to anti-RANK, anti-RANKL and anti-OPG antibodies in 10 fields. Moreover, according to the proportion between the amount of cells positive for RANKL and OPG, the cases were categorized into: RANKL>OPG, OPG>RANKL e RANKL=OPG. CGCL showed a higher amount of MO (p=0.002) and total cells (p=0.003) both positives to RANKL compared with the PGCL. Additionally, the CGCL revealed a significant association with the ratio of RANKL>OPG (p=0.001). Analysis of the bone resorption factors revealed no significant differences between aggressive and non-aggressive CGCL (p>0.05). It was observed a positive correlation between the markers themselves, and a negative correlation between lesion size and quantity of OPG positive MO cells (p=0,004) and total cells (p=0,009). Through these results, we suggest that the greatest CGCL resorptive potential compared to the PGCL, may have occurred to the high expression of RANKL. Furthermore differences in the biological behavior of aggressive and non-aggressive CGCL appear to be related to the expression of these bone resorption factors

Imunoexpressão de fatores reguladores da osteoclastogênese na doença periodontal em humanos e sua relação com os parâmetros clínicos

Periodontal disease is an infection initiated by oral periodontal pathogens that trigger an immune response culminating in tissue destruction. This destruction is mediated by the host by inducing the production and activation of lytic enzymes, cytokines and the stimulation of osteoclastogenesis. The aim of this study was to compare the immunohistochemical expression of factors involved in bone resorption, RANKL (Ligand Receptor Activator of Nuclear Factor kappa B), OPG (Osteoprotegerin) and TNF-α (tumor necrosis factor alpha) between the gingival healthy, gingivitis and chronic periodontitis and correlate them with clinical parameters. The sample consisted of 83 cases and 12 clinically healthy gums, 42 gingivitis and 29 periodontitis, from 74 adolescent and adult patients with a mean age of 35 years, without systemic changes and non-smokers, predominantly female and race brown. There was no statistically significant difference for the expression of anti-RANKL (p = 0.581) and RANKL / OPG ratio (p = 0.334) when comparing the three conditions, but the anti-OPG and anti-TNF-α showed statistically significant between the types of injury (p = 0.001 and p <0.001, respectively), showing greatest expression in periodontitis. In cases of periodontitis, the variable clinical attachment loss (PIC) was statistically significant and positive correlation, respectively, with immunostaining of anti-RANKL (p = 0.002, p = 0.001 and r = 0.642), anti-OPG (p = 0.018, p = 0.014 and r = 0.451), anti-TNF-α (p = 0.032, p = 0.014 and r = 0.453) and the percentage ratio of RANKL / OPG (p = 0.018, p = 0.002 and r = 0.544). The tooth mobility (MB) showed a statistically significant difference only with immunohistochemical anti-RANKL (p = 0.026), and probing depth (PD) was positively correlated with anti-RANKL (p = 0.028 and r = 0.409), both in cases of periodontitis. Only in cases of gingivitis TNF-α was positively correlated with RANKL (p = 0.012 and r = 0.384) and the RANKL / OPG ratio (p = 0.027 and r = 0.341). Given these results, we conclude that the greatest expression of TNF-α in periodontitis demonstrates a relationship with the progression and severity of periodontal disease and the correlation between all antibodies and clinical attachment loss demonstrates their involvement in periodontal bone resorption

Imunoexpressão de vegf-c, vegfr-3 e hif-1α e mensuração da densidade linfática em carcinomas epidermóides de lábio inferior metastáticos e não-metastáticos: uma relação com parâmetros clinicopatológicos e prognósticos

Squamous cell carcinoma of the lower lip is among the most common malignant tumors of the oral and maxillofacial region, with good prognosis in more than 90% of patients with 5-year survival. In these carcinomas, the development of lymph node metastasis decreases the prognosis and it has been associated with the formation of new lymphatic vessels. It has been suggested the important role of vascular endothelial growth factor-C (VEGF-C), the receptor type 3 VEGF (VEGFR-3) and hypoxia-induced factor 1 (HIF-1) in this process. The aim of this study was to evaluate the immunoexpression of VEGF-C, VEGFR-3 and HIF-1α and correlate with intra and peritumoral lymphatic density in squamous cell carcinomas of the lower lip metastatic and non-metastatic. The sample consisted of 50 cases of squamous cell carcinoma of lower lip, of which 25 had regional lymph node metastasis and 25, absence of metastasis. The percentages of cells immunostained for VEGF-C, VEGFR-3 and HIF-1α in front of tumor invasion and in the center of tumor were evaluated. Microvessel density lymphatic (MDL) was determined by the counting of lymph microvessels immunostained by the anti-D2-40 in five fields (200×), in an area of evaluation with 0.7386 mm2. The invasion of the lymph vessels by malignant cells was also evaluated. Immunostaining was correlated with the presence and absence of metastasis, TNM clinical stage, local recurrence, disease outcome (remission of injury or patient death) and histological grading. The analysis of intra and peritumoral lymphatic density showed no significant association with clinicopathological parameters and immunoexpressions of VEGF-C, VEGFR-3 and HIF-1α (p > 0,05). There was a weak positive correlation, significant, between intra and peritumoral lymphatic density (r = 0,405; p = 0,004). VEGF-C showed no significant association with clinicopathological and prognosis parameters (p > 0,05). For VEGFR-3, there was scarce membrane staining and intense and homogenous cytoplasmic staining in neoplastic cells. Percentage of positive cytoplasmic VEGFR-3 in center of tumor, exhibited a statistically significant association with metastasis (p = 0,009), patient death (p = 0,008) and histological grades of malignancy proposed by Bryne et al. (1992) (p = 0,002) and World Health Organization (p = 0,003). A low positive correlation was statistically significant between the immunoreactivity of VEGFC and VEGFR-3 cytoplasmic (r = 0,358; p = 0,011) and between the percentage of positive cytoplasmic VEGFR-3 in front of tumor invasion and in the center of the tumor (r = 0,387; p = 0,005) was also demonstrated. There was no association between HIF-1α, clinicopathological and prognosis parameters, and VEGF-C and VEGFR-3. The percentage of nuclear positivity for HIF-1α was significantly higher in cases without invasion of peritumoral lymphatic (p = 0,040). Based on the results we can conclude that most cytoplasmic expression of VEGFR-3 in center of tumor in metastatic cases, high degree of malignancy and poorly differentiated, contributes to poor outcome of squamous cell carcinoma of the lower lip, including patient death. Intra and peritumoral lymphatic density seems to be not associated with lymph node metastasis in these carcinomas

Expressão imuno-histoquimica de proteínas relacionadas com a reabsorção óssea em carcinoma epidermoide de palato duro e língua

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Perfil imuno-histoquímico do infiltrado inflamatório no front de invasão em carcicomas epidermóides de língua e lábio inferior

The progression of the oral squamous cells carcinomas (OSCCs) seems to suffer influence from related factors to the host, as local and systemic immunologic response, which are essential to the antineoplasic defenses. The purpose of this study was evaluate the local immunity in 30 tongue and 20 lower lip SCC by immunohistochemistry method, utilizing antibodies anti-CD3, CD4, -CD8, -CD25 e -ζ(zeta), which immunoexpressions were compared considering the anatomical localization, the intensity of the inflammatory infiltrate into the front of invasion and metastases. The CD4/CD8+ ratio was calculated for each case and associate with the mentioned variable, being the intensity of the inflammatory infiltrated also compared with the anatomical localization and metastase and for this the cases had been grouped in two categories: (n = 10) absent/scarce inflammatory infiltrate; and (n = 40) moderate/intense infiltrate. Fisher´s exact test was performed (α= 0.05) and it was not observed any significant correlation between these groups with anatomical sites and metastases. With regard to the immunoexpression, the CD3+, CD4+, CD8+ and CD25+ cells count was higher in the lower lip SCCs while the anti-ζimmunomarcation was more evident in the non metastatic cases. Through the statistical analyses, it was verified that the CD3 exhibited positive-significant correlation with the inflammatory infiltrate (p = 0.023). Furthermore, antibodies against CD8 and CD25 cells were also significantly correlated with the inflammatory infiltrate (p = 0.002 and 0.030, respectively) and with the anatomical site (p = 0.004 and p = 0.004) mainly in the lower lip SCCs. CD4/CD8 ratio did not show significant association with metastase nor with anatomical localization. We conclude that the inflammatory infiltrated of the Bryne s (1998) system did not constitute an indicator of aggressiveness in the tongue and lower lip SCCs analyzed and that clinical behavior of the SCCs studied was related in part to the immunohistochemical profile of infiltrated the inflammatory present in tumoral invasion front