RESUMEN
OBJECTIVE: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. METHODS: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). RESULTS: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=-0.533, p=0.01). CONCLUSIONS: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.
Asunto(s)
Acromegalia/tratamiento farmacológico , Acromegalia/metabolismo , Adenoma/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Adenoma Hipofisario Secretor de Hormona del Crecimiento/tratamiento farmacológico , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Cuidados Preoperatorios , Somatostatina/farmacología , Acromegalia/patología , Acromegalia/cirugía , Adenoma/metabolismo , Adenoma/patología , Adenoma/cirugía , Adulto , Proliferación Celular/efectos de los fármacos , Estudios Transversales , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Retrospectivos , Somatostatina/administración & dosificación , Somatostatina/análisisRESUMEN
INTRODUCTION: Giant cell tumors (GCT) are benign, but locally aggressive primary bone neoplasms, that frequently occur in the epiphyses of the long bones. Less than 1% of all GCTs primarily involve the skull where they are preferentially seen in the sphenoid and temporal bones. In the pediatric age group they are exceptionally rare. CASE REPORT: The authors report the management of a GCT involving the frontal bone in an 18-month-old girl. The patient underwent wide surgical excision of the lesion and remains free of clinical and radiological evidence of tumoral recurrence thirty months after treatment. CONCLUSION: Although rare, GCTs should be taken into consideration as a differential diagnosis of rapidly enlarging cranial mass lesions in pediatric patients. Gross total surgical excision eliminates the potential risks of adjuvant radiotherapy. However, considering the aggressive nature and potential malignancy of these lesions, careful long-term clinical and imaging follow-up is recommended.