Expression of DNA toposiomerase I and DNA topoisomerase II-alpha in testicular seminomas.
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.
Coleman
L W
LW
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, USA.
Perkins
S L
SL
Bronstein
I B
IB
Holden
J A
JA
D000328:Adult; D002455:Cell Division; D004264:DNA Topoisomerases, Type I / Q000032:analysis / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000032:analysis; D016256:Lewis X Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D018239:Seminoma / Q000201:enzymology* / Q000473:pathology; D013736:Testicular Neoplasms / Q000201:enzymology* / Q000473:pathology
D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D017730:Ki-1 Antigen; D016256:Lewis X Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases