Heparanase-1 and components of the hedgehog signalling pathway are increased in untreated alveolar orbital rhabdomyosarcoma

To assess the activities of heparanase-1 and elements of the hedgehog signalling pathway in alveolar orbital rhabdomyosarcoma.Specimens (n = 23) were divided into two groups, those from patients with preoperative chemoradiotherapy or untreated patients; six samples of normal extraocular muscle were used as a normal muscle group. The presence of heparanase-1, patched, smoothened and glioma-associated oncogene homologue-1 protein expression was determined in 23 cases of archival paraffin-embedded alveolar orbital rhabdomyosarcoma after immunohistochemistry. RNA was extracted from three groups of paraffin-embedded specimens and messenger RNA expressions of heparanase-1, smoothened and glioma-associated oncogene homologue-1 compared using nested reverse transcriptase polymerase chain reaction and a limiting dilution analysis.The heparanase-1, patched, smoothened and glioma-associated oncogene homologue-1 protein was expressed in 91.3%, 87.0%, 91.3% and 78.3%, respectively, of the alveolar orbital rhabdomyosarcoma specimens. Untreated rhabdomyosarcoma samples tended to stain intensely, but staining was relatively weak in tissue obtained from the chemoradiotherapy group. The expression levels of heparanase-1, smoothened and glioma-associated oncogene homologue-1 messenger RNA in untreated and chemoradiotherapy groups paralleled that seen with immunology, and there were no significant differences in heparanase-1, smoothened and glioma-associated oncogene homologue-1 messenger RNA levels between the chemoradiotherapy group and the normal muscle group (P0.05). However, the messenger RNA in the untreated group were all significantly higher than those in the chemoradiotherapy and normal muscle groups (P0.01).Both heparanase-1 and hedgehog signalling pathway are involved in the pathogenesis of alveolar orbital rhabdomyosarcoma; however, chemotherapy and/or radiotherapy appears to significantly inhibit their upregulation.