RESUMO
A next-generation FISH probe mapping to the MDM2 locus-specific region has recently been designed. The level of MDM2 gene amplification (high versus low) may allow selection of patients for cancer treatment with MDM2 inhibitors and may predict their responsiveness. We investigated the spectrum of MDM2 gene alterations using the new probes in vivo after visualizing single neoplastic cells in situ from a series of glioblastomas. Signals from next-generation repeat-free FISH interphase probes were identified in tissue microarrays that included 3 spots for each of the 48 cases. The murine double minutes (MDM2)-specific DNA probe and the satellite enumeration probe for chromosome 12 were used. Three cases (6%) showed more than 25 signals (high gene amplification), and 7 (15%) showed 3-10 signals (gains); among these, 4 cases (8%) had an equal number of MDM2 and centromeric signals on chromosome 12 (polyploidy). Genomic heterogeneity was observed only in 3 cases with low gene amplification. In our series, 6% of glioblastomas exhibited high MDM2 amplification (in vivo) with a pattern related to the known double minutes/chromothripsis phenomenon (in situ), and only cases with low amplification showed genomic heterogeneity. We concluded that the rate of MDM2 gene amplification can be a useful predictive biomarker to improve patient selection.
Assuntos
DNA de Neoplasias/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sondas de DNA , Feminino , Amplificação de Genes , Glioblastoma/patologia , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Análise Serial de Tecidos , Adulto JovemRESUMO
BACKGROUND: Solid pseudopapillary tumors of the pancreas are rare exocrine pancreatic tumors. Through a review of pediatric cases in a single Institution, we present the clinical and surgical management of this neoplasm. METHODS: We retrospectively reviewed the clinical charts of patients treated at our unit between 1995 and 2009 for SPT. Clinical and surgical management were analyzed and reported. RESULTS: During the study period 11 patients underwent surgery for pseudopapillary tumor. Five patients were treated with duodenum-preserving pancreatic head resection and six patients with splenopancreasectomy with a Roux-en-Y pancreatic jejunostomy. Patients did not show recurrence and are currently disease free. Blood tests, Ultrasound, Computed tomography and Magnetic Resonance Imaging were not useful to preoperatively identify the nature of the pancreatic masses. CONCLUSION: Solid pseudopapillary tumor is a rare condition that should be taken into account for the differential diagnosis of pancreatic masses in pediatric age. Due to its favourable prognosis, surgical removal should be planned and done following the intraoperative findings.
