DNA topoisomerase I and IIalpha expression in penile carcinomas: assessing potential tumour chemosensitivity.
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.
Berney
Daniel M
DM
The Orchid Tissue Laboratory, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. danberney@hotmail.com
Stankiewicz
Elzbieta
E
Adlan
Ahmed M A
AM
Kudahetti
Sakunthala
S
Biedrzycki
Olaf J
OJ
Hadway
Paul
P
Watkin
Nick
N
Corbishley
Cathy
C
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
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