TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

Polioencephalomalacia in Buffaloes in the Amazon Biome.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes in the Amazon biome are described. Epidemiological data were obtained during the clinical visit in which buffalos were submitted to an examination of the nervous system. The diagnosis of PEM was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. In the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), with decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding with the corral structures, head pressing and circumduction of the hindquarters when supported on the thoracic limbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes, and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. A histopathological examination showed laminar necrosis of the cerebral cortex. The cause of PEM in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, particularly in the Amazon region.

Associations of VEGFA and KDR single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas.

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.

Correlação da imunoexpressão do fator de choque térmico 1 (hsf1) com aspectos clinicopatológicos em carcinomas de células escamosas de língua oral / Immunoexpression correlation of heat shock factor 1 (HSF1) with clinicopathological features in squamous cell carcinomas of tongue

O carcinoma de células escamosas oral apresenta altas taxas de morbidade e mortalidade na população, com isso, enormes esforços estão sendo feitos para categorizar alterações morfológicas e identificar biomarcadores que tenham valor prognóstico, bem como que estratifiquem os pacientes em opções terapêuticas individualizadas. Nessa perspectiva, destaca-se o fator do choque térmico 1 (HSF1), o qual é um fator de transcrição de proteínas do choque térmico (HSPs) que permite ao câncer lidar com estressores associados à malignidade, atuando de diferentes formas na progressão tumoral. Esta pesquisa objetivou realizar a análise clinicopatológica de 70 casos de carcinoma de células escamosas de língua oral (CCELO) e o estudo imunoistoquímico dos níveis de expressão da proteína HSF1 em CCELO em comparação com 30 espécimes de mucosa oral normal (MON), correlacionando-se, ainda, esta imunoexpressão com aspectos clinicopatológicos do CCELO.

Quanto aos casos de CCELO, 57,1% exibiram estadiamento clínico III ou IV, 82,9% foram gradados como de alto grau segundo Bryne (1998) e 47,1% como de alto risco de malignidade segundo Brandwein-Gensler et al., (2005). Foi observada uma taxa de sobrevida livre de doença de 47,84% e taxa de sobrevida global de 68,20% nos casos analisados e que o alto grau de malignidade segundo a Gradação de Bryne (1998) (p= 0,05) e tamanho do tumor T3 ou T4 (p= 0,04), recidiva local (p= 0,02) e invasão perineural (p= 0,02) determinaram impactos negativos nesses tempos de sobrevida. Estes resultados corroboram as informações consolidadas na literatura quanto à influência negativa de alguns indicadores clinicopatológicos na sobrevida dos pacientes com CCELO. Encontrou-se resultado estatisticamente significativo (p<0,01) quando comparou-se a imunoexpressão de HSF1 entre a MON e o CCELO. Esta significativa maior expressão de HSF1 nos casos de CCELO sugere que esta proteína atue, de fato, no processo de patogênese desta lesão. Entretanto, não foram encontradas associações estatisticamente significativas entre esta superexpressão com os parâmetros clínicopatológicos analisados. Esse achado pode refletir a influência de eventos epigenéticos sobre o gene HSF1 ou uma possível estabilidade da expressão desta proteína ao longo da progressão da doença. (AU)

Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score.

Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression. (AU)

Polimorfismos das isoformas M1, T1 e P1 da glutationa S-transferase e associação com os aspectos clínico-patológicas no carcinoma colorretal / Polymorphism of glutathione S-transferase M1, T1 and P1 and association with clinicopathological aspects in colorectal carcinoma

As variáveis clínico-patológicas são importantes fatores que possam estar associados à progressão da neoplasia e, consequentemente, ao prognóstico da doença. As glutationas S-Transferases GSTM1, GSTT1 e GSTP1 são enzimas da segunda fase de biotransformação que atuam na destoxificação de uma ampla variedade de agentes exógenos incluindo os carcinógenos. Os genes GSTM1, GSTT1 e GSTP1 são polimórficos em humanos e suas variantes têm sido associadas, em algumas populações, ao aumento dos riscos de neoplasia, entre elas o carcinoma colorretal. Neste estudo retrospectivo 50 biópsias de pacientes com carcinoma colorretal do Rio Grande do Sul foram analisadas os polimorfismos nos genes GSTM1, GSTT1 e GSTP1 por PCR multiplex e RFLP, quanto às variáveis clínico-patológicas: localização, estadiamento e diferenciação. Não foram encontrados valores p significativo nas variáveis: estadiamento (p=0,28, p=0,93 e p=0,67), diferenciação (p=0,70 e p=0,37) e localização (p= 0,23. p= 0,58 e p= 0,60 ) respectivamente e o presença do polimorfismos dos genes GSTM1, GSTT1 e GSTP1 nas variáveis estadiamento e localização. A única variável clínico-patológica que apresentou valor significativo na diferenciação do CCR foi o polimorfismo do gene GSTP1 Ile/val e val/val (p= 0,046) entretanto, mais pesquisas são necessárias para confirmar estes achados ,visto que, esses resultados podem ter sido influenciados pelo número reduzido de biópsias analisadas.

The clinical and pathological variables are important factors that may be associated with tumor progression and consequently, the prognoses of the disease. The glutathione S-Transferases GSTM1, GSTT1 and GSTP1 are enzymes from the second phase II of biotransformation that work in the detoxificatin pathways of a wide range of exogen agents including the carcinogens. The GSTM1, GSTT1 and GSTP1 genes are polymorphic in humans and their variants have been related in some populations an increased neoplasia risks, including colorectal cancer. In this retrospective study 50 biopsies of patients with colorectal carcinoma of South Brazilian were analyzed polymorphisms in the genes GSTM1, GSTT1 and GSTP1 by Multiplex PCR and RFLP for the clinical and pathological variables: location, stage and differentiation. There were no significant p values for the variables: stage (p=0,28, p=0,93 e p=0,67), differentiation (p=0,70 e p=0,37) and location (p= 0,23. p= 0,58 e p= 0,60 ) respectively and the presence of polymorphism of GSTM1, GSTT1 and GSTP1 in variables staging and location. The only clinicopathological variable that showed significant value in the differentiation of CCR was the polymorphism GSTP1 ile/val and val/val (p= 0,046), however, more research is needed to confirm these findings, since these results may have been influenced by the reduced number of biopsies analyzed.