Histology-specific expression of a DNA repair protein in pediatric rhabdomyosarcomas.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Thomson
B
B
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA. bthomson@iupui.edu
Tritt
R
R
Davis
M
M
Kelley
M R
MR
D000293:Adolescent; D001711:Biotransformation / Q000502:physiology; D019757:Carbon-Oxygen Lyases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D003630:Daunorubicin / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D005246:Feedback; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010084:Oxidation-Reduction; D018232:Rhabdomyosarcoma, Alveolar / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016037:Single-Blind Method; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D014157:Transcription Factors; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003630:Daunorubicin