Histology-Specific Expression of a DNA Repair Protein in Pediatric Rhabdomyosarcomas

DNA repair enzymes have a critical role in cellular maintenance and survival. The enzyme apurinic/apyrimidinic endonuclease/redox factor 1 (APE/ref1), a key protein in the base excision repair pathway, displays both repair and redox control. We examined the role of APE/ref1 in pediatric embryonal and alveolar rhabdomyosarcomas (ARMS).Using an immunohistochemical method, fixed tissue from 31 newly diagnosed pediatric rhabdomyosarcomas were evaluated for expression of APE/ref1. Tissue was obtained from Indiana University and the Cooperative Human Tissue Network.We demonstrated high levels of expression within the localized and metastatic embryonal rhabdomyosarcomas. This contrasted with both localized and metastatic ARMS, which had low levels of APE/ref1 expression. This histology-specific difference proved to be significant (P = 0.003). Furthermore, the expression within all tumors examined was localized to the nucleus and did not differ between localized and metastatic tumors.We propose several hypotheses to explain this histology-specific expression of APE/ref1 in pediatric rhabdomyosarcomas. Because the majority of ARMS expressed either the PAX3/FKHR or PAX7/FKHR fusion transcript, the low level of expression may be related to the redox activity of APE/ref1. The low levels may also be related to the bioreductive activity of APE/ref 1.