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.
Patients and 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.
Conclusion: 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.