RESUMO
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Genômica , Humanos , Recidiva Local de Neoplasia/genéticaRESUMO
PURPOSE: To evaluate the role of neuro-imaging in children presenting with the first afebrile seizure and determine factors that influence the outcome of imaging in a large paediatric emergency centre. METHOD: This is a retrospective review of the medical records of all patients presenting with the first non-febrile seizure to a large paediatric emergency centre in the state of Qatar. Seizure classification followed the current ILAE classification system. Imaging was undertaken in our tertiary hospital and all images were reviewed by experienced neuro-radiologists. Student t test was used for statistical analysis. RESULTS: Ninety-six children underwent neuro-imaging following the first afebrile seizure. Of them, thirty-two patients (33%) were reported to have abnormalities. Children below the age of two demonstrated a significantly higher percentage of abnormal imaging (59%); (p=0.002). Children presenting with prolonged seizures showed a high percentage of imaging abnormalities (58%); (p=0.003). Children with focal seizures demonstrated a higher percentage of imaging abnormality compared to those presenting with generalized seizures (35% vs 31%). This difference did not reach statistical significance. CONCLUSION: Children below the age of two demonstrated significantly higher percentages of abnormal imaging (59%), as did children presenting with status epilepticus (58%). Neuro-imaging should be considered in infants and those with focal or prolonged seizures. Neuro-imaging informed decision making in 6-8% of children.
