RESUMO
Sessile serrated adenomas are now recognised as precursor lesions of a substantial subset of colorectal cancers arising via a so-called "serrated pathway". However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas and conventional adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using quantitative real-time polymerase chain reaction on cathepsin E (CTSE) demonstrated a significantly (p < 0.05) higher expression in sessile serrated adenomas as compared to hyperplastic polyp and tubular adenomas. Trefoil Factor 1 showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas, while staining in tubular adenomas and hyperplastic polyps was absent or weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (p < 0.05). This study demonstrates the over-expression in CTSE, in particular, and TFF1 in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas.
Assuntos
Adenoma/genética , Biomarcadores Tumorais/análise , Catepsina E/biossíntese , Neoplasias Colorretais/genética , Proteínas Supressoras de Tumor/biossíntese , Adenoma/metabolismo , Adenoma/patologia , Idoso , Catepsina E/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Pólipos Intestinais/genética , Pólipos Intestinais/metabolismo , Pólipos Intestinais/patologia , Masculino , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator Trefoil-1 , Proteínas Supressoras de Tumor/genética , Regulação para Cima , Proteínas ras/genéticaRESUMO
AIMS: To correlate the presence or absence of a factor XI gene mutation with factor XI activity in patients with severe or partial reduction in factor XI. METHODS: Patients previously found to have reduced factor XI levels were recalled for repeat testing and factor XI genetic analysis. Also, during the 18 month study period, any routine patient found to have an isolated reduced or low normal factor XI level had factor XI genetic analysis. RESULTS: Twenty-two cases were studied and 11 with factor XI from <2 to 57 U/dL (reference 55-130 U/dL), were found to have a factor XI gene mutation. Gene sequencing identified 15 different mutations, with four patients found to be compound heterozygotes. One patient with no bleeding history had a novel polymorphism which family studies showed was not associated with his low factor XI. No factor XI gene abnormality was detected in 10 patients and they have either acquired causes of deficiency or factor XI levels in the lower portion of the normal range. CONCLUSION: Genetic analysis of the factor XI gene is important to confirm or exclude inherited causes of factor XI deficiency, especially when the reduction is mild.
Assuntos
Análise Mutacional de DNA/métodos , Deficiência do Fator XI/diagnóstico , Deficiência do Fator XI/genética , Fator XI/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Criança , Deficiência do Fator XI/sangue , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Heterozigoto , Humanos , Masculino , Valores de Referência , Austrália do SulRESUMO
We report on a cross-laboratory study of type 2N von Willebrand disease (vWD). We tested 101 selected plasma samples for factor VIII and factor VIII binding activity of von Willebrand factor (vWF). Of these plasma samples, 31 were cotested by 2 specialist centers using different detection procedures for vWF-factor VIII binding: there was good agreement between results obtained by chromogenic assay and enzyme-linked immunosorbent assay. In total, 8 patients with type 2N vWD were identified. The 2-stage factor VIII assay detected a deficiency of factor VIII relative to vWF antigen in all 8 patients; the 1-stage factor VIII assay detected a relative deficiency in only 3 patients. Four patients were homozygous for the most common type 2N mutation (R854Q), 3 patients were presumed to be compound heterozygotes, and in 1 patient no type 2N mutations were identified. In this study of patients from 5 specialist centers in Australia, type 2N vWD was found in 5 families. The 2-stage factor VIII assay was more useful as a screening test than the 1-stage assay, and both vWF-factor VIII binding assays were equally effective.
