Different pattern of matrix metalloproteinases expression in alveolar versus embryonal rhabdomyosarcoma

Abstract

Background/purpose The matrix metalloproteinases (MMPs), a family of enzymes that degrade the extracellular matrix (ECM), are important in neoplastic cell invasion and metastasis. Data for rhabdomyosarcoma (RMS), the most frequent soft tissue sarcoma of childhood, are lacking. The aim of this study was to assess their expression in this tumor and to evaluate the correlation with clinicopathologic parameters. Methods Immunohistochemical expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, and TIMP-2 was investigated in 33 human RMSs, 12 alveolar, and 21 embryonal histologic subtypes (12 high risk and 9 low/standard risk). Evaluation of the results was based on the percent of positive neoplastic cells and on staining intensity (negative, moderate, and strong). In situ zymography was carried out on 4 frozen RMS samples (2 alveolar and 2 high-risk embryonal). Results Alveolar type showed a stronger MMP-1, -2 and -9 expression in comparison with embryonal ( P = .006, P <.001, and P <.001, respectively). Intratumoral vessels and perivascular ECM were positive for MMP-9 in the majority of RMSs. Both TIMPs had negative results. Conclusions Gelatinases MMP-2 and MMP-9 and collagenase MMP-1 overexpression seem to contribute to the more aggressive phenotype of alveolar rhabdomyoblastic cells. Further characterization of the expression of MMPs and consequent utilization of their inhibitors in aggressive alveolar RMSs might lead to the development of novel anticancer therapies.