DNA topoisomerase I (
topo I) is the molecular target of the
camptothecin group of anticancer drugs. These drugs are S-phase specific and require elevated
topo I for
tumor cell killing. To determine whether increased
topo I expression occurs in testicular
seminomas, 20 cases of testicular
seminoma were retrieved from the surgical pathology files at the University of Utah Health Sciences Center and stained with an antibody that recognizes
topo I in
paraffin embedded human tissue sections.
Topo I elevation was observed in 30% (6/20) of the
seminomas. Because the response to
topo I targeted drugs requires cell proliferation, the proliferative index of the
seminomas was determined by immunohistochemical staining for
DNA topoisomerase II-alpha (
topo II-alpha) a new marker of cell proliferation. AU
seminomas had easily detectable
topo II-alpha. The average
topo II-alpha index of the 20 cases was 52.1 +/- 15.3.
Seminomas with elevated
topo I had an average
topo II-alpha proliferative index of 60.8 +/- 17.5 and
seminomas with normal
topo I expression had a
topo II-alpha proliferative index of 48.4 +/- 13.2. This is significantly different at the 0.05% confidence level. Focal expression of CD30 was seen in 60% (12/20) of the
neoplasms. None of the cases showed positive staining for CD15 and c-erbB-2. Our results suggest that chemotherapeutic protocols involving topoisomerase targeting drugs might be useful against testicular
seminomas.