Topoisomerase II alpha expression in testicular germ cell tumors.
OBJECTIVE
Inhibitors of topoisomerase II alpha (TopoIIalpha), an enzyme with a crucial role in DNA maintenance, are included in the chemotherapy protocols for testicular germ cell tumors (GCTs). Despite the success of current chemotherapy regimens, a significant number of patients experience relapse. We analyzed TopoIIalpha expression in primary and metastatic testicular GCTs because this enzyme is a target for some antineoplastic agents.


METHODS
Primary GCT specimens from 109 patients, including 57 seminomas and 52 mixed GCTs (41 embryonal carcinomas, 23 yolk sac tumors, 19 seminomas, 8 choriocarcinomas, 17 teratomas with immature elements, and 16 teratomas with mature elements), were obtained from our archives. The metastatic lesions from 11 of the patients with mixed GCTs included seven teratomas with mature components, five embryonal carcinomas, one yolk sac tumor, one choriocarcinoma, and one teratoma with immature components. Representative sections were subjected to immunohistochemistry with monoclonal antibody against TopoIIalpha, and the nuclear staining findings were evaluated.


RESULTS
Most embryonal carcinoma (100%), yolk sac tumor (95%), seminoma (88%), and choriocarcinoma (62%) components of the GCTs were TopoIIalpha immunoreactive. None of the teratoma specimens with mature elements expressed TopoIIalpha.


CONCLUSIONS
The results of our study have shown that TopoIIalpha is expressed in most seminomas, embryonal carcinomas, yolk sac tumors, and choriocarcinomas, suggesting a possible mechanism of sensitivity of these components to TopoIIalpha inhibitors. Teratomas with mature and immature elements expressed low levels of TopoIIalpha, which might contribute to their chemoresistance. These findings imply that the variable chemoresponsiveness of testicular GCTs could have an underlying molecular basis.
Dimov
Nikolay D
ND
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Zynger
Debra L
DL
Luan
Chuanyan
C
Kozlowski
James M
JM
Yang
Ximing J
XJ
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018236:Carcinoma, Embryonal / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002822:Choriocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018240:Endodermal Sinus Tumor / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D012494:Sampling Studies; D018239:Seminoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D012680:Sensitivity and Specificity; D013724:Teratoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II