RESUMO
AIMS: The presence of a BRAF mutation is a strong marker for poor prognosis of colorectal carcinoma (CRC), and can be used as evidence of a sporadic mechanism of mismatch repair deficiency. BRAF mutation may also predict resistance to EGFR-targeted therapy. A BRAF V600E-specific antibody has recently become commercially available. The aim of this study was to determine whether immunohistochemistry can predict BRAF mutations in CRC. METHODS AND RESULTS: Immunohistochemistry was performed on 52 genotyped CRC cases (17 BRAF mutant, 18 KRAS mutant, 17 BRAF/KRAS wild-type) with monoclonal antibody VE1. Cytoplasmic staining was observed in 71% of BRAF V600E mutant tumours (moderate or strong staining in 50% of these cases). Weak cytoplasmic staining was observed in 17% of KRAS mutant tumours and 35% of wild-type tumours. Non-specific nuclear staining was common. The sensitivity and specificity of immunohistochemistry with VE1 for BRAF mutation were 71% and 74%, respectively; when only moderate or strong staining was considered to be positive, the specificity was 100%, but the sensitivity only 35%. CONCLUSIONS: Immunohistochemistry with VE1 is not a useful surrogate for genotyping in CRC. Although moderate or strong cytoplasmic staining is specific for BRAF V600E mutations, this antibody is insufficiently sensitive to serve as an effective screening tool.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Proteínas Mutantes/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/imunologia , Proteínas Mutantes/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas B-raf/imunologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
PURPOSE: To describe, in a group of patients with moderately advanced retinitis pigmentosa (RP), the prevalence of cystoid macular edema (CME), the variation in foveal thickness over a 48-week period, the correlation of visual acuity (VA) with retinal thickness, and the lack of response of CME to lutein administration. METHODS: Optical coherence tomography (OCT) imaging of the macula and clinical examination were evaluated for 77 eyes of 39 patients with RP over 11 months, with a scan done every 6 weeks. RESULTS: The prevalence of CME, defined by cysts visible on OCT, was 49%. Bilateral CME was present in 44% of patients (17 of 39), and an additional two patients had unilateral CME. Central retinal thickness varied little over the 48 weeks. Sixty-six percent of the eyes with CME had VA of 20/40 or better. The eyes with CME with VA worse than 20/40 had either greater degrees of thickening or in fact had lower thickness measures. For the eyes without CME, the eyes with VA worse than 20/40 tended to have lower retinal thickness than the eyes with VA of 20/40 or better. VA was highly concordant between eyes, and did not differ significantly between the groups with and without CME. Lutein did not show a statistically significant effect on retinal thickness in the patients with or without CME, nor was such an effect observed in subgroups of patients with vision better or worse than 20/40. CONCLUSION: The prevalence rate of CME is higher than in previous reports, perhaps because the patients had some preserved macular vision and because of the use of a definition based on OCT findings. Retinal thickness remains fairly stable over time, both in eyes with CME and in eyes without CME.
