Identification of epithelial-mesenchymal transition markers (EMT) by immunohistochemistry in pediatric osteosarcoma and association with clinical outcomes

Abstract

The epithelial-mesenchymal transition (EMT) is the ability of epithelial and mesenchymal cells to exchange phenotypes transiently. Its identification in carcinomatous cells has been associated with aggressive clinical phenotypes. In sarcomas, this ability is under study. 

Objective: to evaluate the expression of two transcription factors involved in EMT by immunohistochemistry in pediatric osteosarcoma and its association with clinical outcomes. 

Patients and Method: A retrospective cohort study in children under 18 years of age with osteosarcoma diagnosis. Immunohistochemistry was performed for Snail and Twist-1 expressions from samples collected at the time of diagnosis. Correlations between immunohistochemistry and the clinical outcomes and overall survival were perfo med. 

Results: 53 patients were included. There were 26 positive cytoplasmic cases (49.1%) in Snail expression and were correlated with the presence of multiple metastases (p = 0.02) and distant bone metastases (p = 0.01). On the other hand, 45 cases (84.9%) were positive in Twist-1 expression in the nuclear location, showing no association with the analyzed clinical variables. 

Conclusions: Snail and Twist-1 were frequently expressed in pediatric cases of osteosarcoma. Cytoplasmic Snail was correlated with the presence of multiple metastatic disease and distant bone metastases. The positivity of both markers suggests the activation of these proteins as regulators of EMT events in this tumor, suggesting a role in the phenomena related to the clinical presentation of the disease.