title: DNA topoisomerase I and IIalpha expression in penile carcinomas: assessing potential tumour chemosensitivity.
abstract: OBJECTIVE
  To examine the tissue expression of DNA topoisomerase I (Topo I) and IIalpha (Topo II), to pursue the possibility of future chemotherapy regimens for squamous cell carcinoma of the penis (SCCP), as high expression of Topo I might indicate sensitivity to the camptothecins, whereas high Topo II might indicate sensitivity to etoposide.
  
  
  METHODS
  In all, 73 patients with SCCP were reviewed and then tissue samples microarrayed. These were then stained with immunohistochemistry for Topo I, Topo II and Ki-67. Tumour stage, grade and type were available.
  
  
  RESULTS
  Topo II showed a strong positive correlation with the proliferation index as measured by Ki-67 (P < 0.001) but no correlation with Topo I. There were also strong correlations between tumour grade and Ki-67, and Topo II expression (both P < 0.001). Tumour type was also strongly correlated with Topo II and Ki-67 expression, with the highest expression in basaloid carcinomas and the lowest in verrucous carcinomas. However, Topo I expression was not correlated with any other tumour variable.
  
  
  CONCLUSIONS
  The expression of Topo I is grade- and type-independent, and chemotherapy using the camptothecins is unlikely to be effective. The strong positivity of Topo II in high-grade and basaloid SCCPs suggests that treatment with etoposide or other Topo II 'poisons' might be a better target for future clinical trials.
authors.affiliation: The Orchid Tissue Laboratory, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. danberney@hotmail.com
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: Ahmed M A
authors.initials: AM
authors.lastname: Adlan
authors.forename: Sakunthala
authors.initials: S
authors.lastname: Kudahetti
authors.forename: Olaf J
authors.initials: OJ
authors.lastname: Biedrzycki
authors.forename: Paul
authors.initials: P
authors.lastname: Hadway
authors.forename: Nick
authors.initials: N
authors.lastname: Watkin
authors.forename: Cathy
authors.initials: C
authors.lastname: Corbishley
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D010412:Penile Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II