Correlation between Topo II alpha expression and chemosensitivity testing for Topo II-targeting drugs in gynaecological carcinomas.
BACKGROUND
The purpose of this study was to investigate the correlation between topoisomerase II alpha (Topo II alpha) expression and the chemosensitivity to Topo II-targeting drugs in gynaecological carcinomas.


METHODS
We analysed the expression of Topo II alpha, and then correlated this with the in vitro chemosensitivities of 43 gynaecological tumors using immunohistochemistry and a tetrazolium dye (MTT) assay.


RESULTS
There was a significant correlation between the Topo II alpha index (the number of positive cells per 100 cells: %) and the tumor cell growth inhibition rate in culture (I.R.: %) for doxorubicin and etoposide (r = 0.631, p < 0.001 and r = 0.645, p < 0.001, respectively). The I.Rs for doxorubicin and etoposide in endometrial carcinomas were lower than those in ovarian carcinomas [38.2 +/- 22.8 vs 54.6 +/- 29.8, 37.3 +/- 19.8 vs 59.3 +/- 30.6] (p < 0.05, respectively). Furthermore, the number of high Topo II alpha index (over 30%) tumors in the ovarian carcinoma cases was higher than that in the endometrial carcinoma cases (63.1% vs 45.8%, p < 0.05).


CONCLUSIONS
Our data suggest that the Topo II alpha index of a tumor is a reflection of its chemosensitivity to Topo II-targeting drugs. The use of this index may enable prediction of a clinical response to chemotherapy using Topo II-targeting drugs in gynaecological malignancies.
Koshiyama
M
M
Department of Obstetrics and Gynaecology, Tenri Hospital, Tenri, Nara, Japan.
Fujii
H
H
Kinezaki
M
M
Yoshida
M
M
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin