Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation

FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01–3.66; p=0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p=0.019) and advanced TNM staging in TN (τ = 0.23; p=0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = −0.47; p=0.018) and lower histological grade (τ = 0.39; p=0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = −0.15; p=0.009) and higher Ki-67 (τ = 0.43; p=0.036) in HER2+ and advanced staging in TN (τ = 0.29; p=0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = −0.54; p=0.005) and staging (τ = −0.29; p=0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead transcription factor 3) is a marker of regulatory T cells (Tregs), whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548) and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction). Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06) in relation to TNBC susceptibility. Most of the patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026). In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples

Intussuscepção em adulto - Relato de um caso

  Apresentação de caso de paciente portadora de intussuscepção intestinal, cuja causa era um pseudo tumor inflamatório de jejuno. O diagnóstico de certeza somente foi realizado por laparotomia e exame histopatológico da peça cirúrgica. São tecidos comentários sobre a entidade, após breve revisão bibliográfica

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC

Nimesulide-induced fatal acute liver failure in an elderly woman with metastatic biliary adenocarcinoma. A case report

CONTEXT:Nimesulide is a selective inhibitor of the enzyme cyclooxygenase 2. Although considered to be a safe drug, cases of acute hepatitis and fulminant liver failure have been reported in Europe, the United States and South America, especially among elderly female patients. Until now, there had not been any reports in the literature relating to Brazilian subjects.CASE REPORT:An 81-year old female who had been using nimesulide therapy for six days presented hematemesis and epistaxis two days before hospitalization. Clinical examination showed an extensive coagulation disorder, diffuse hematomas, hypotension and tachypnea. Laboratory tests revealed abnormalities in coagulation tests; leukocytosis; reduced platelet, hemoglobin and red blood cell counts; and elevated direct bilirubin, serum aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase and renal function biomarkers. Hepatitis B and C tests were not reactive. Carcinoembryonic antigen (CEA), CA-19-9 and CA-125 levels were increased by, respectively, 1,000, 10,000 and 13 fold, whereas the alpha-fetoprotein level was normal, thus indicating a malignant tumor in the bile duct that did not originate from the liver. Thirty-six hours after hospitalization, the patient's condition worsened, leading to death. The necropsy findings included acute hepatitis with hepatocellular collapse, as well as metastasis of a carcinoma, probably from the bile duct.CONCLUSION:Despite the carcinoma presented by the patient, nimesulide use may have contributed towards the fatal acute liver failure. Until this issue has been clarified, caution is required in prescribing nimesulide for liver disease patients