Immunohistochemical expression of topoisomerase IIalpha (Topo IIalpha) and multidrug resistance-associated protein (MRP), plus chemosensitivity testing, as chemotherapeutic indices of ovarian and endometrial carcinomas.
OBJECTIVE
The purpose of this study was to investigate the chemosensitive and chemoresistant indices of gynecologic malignancies.


METHODS
We studied the expression of topoisomerase II alpha(Topo II alpha) and multidrug resistance-associated protein (MRP), and then correlated them with the in vitro chemosensitivities of gynecologic tumor cells using immunohistochemistry and a tetrazolium dye (MTT) assay.


RESULTS
In the 19 ovarian carcinomas examined, the mean Topo II alpha index (%) and the tumor cell growth inhibition rate (I.R.: %) for doxorubicin and etoposide in the clear cell adenocarcinomas [15.8, 21.4, 32.3] were all lower than in the endometrioid [33.9; p<0.001, 58.3, 61.9; p<0.05, respectively] and serous adenocarcinomas [43.6; p<0.001, 75.0, 79.8; p<0.01, respectively]. Comparing these markers with the clinical response to chemotherapy, the overall predictive accuracy of the Topo II alpha index and the MTT assay was 87.5% (14/16) and 81.3% (13/16), respectively. In the 24 endometrial carcinomas examined, the mean Topo II a index and the I.R for doxorubicin and etoposide in the G1 carcinomas [22.2, 26.8, 21.5] were significantly lower than in the G2/G3 carcinomas [38.4, 54.0; p<0.001, 40.5; p<0.05]. Furthermore, strong MRP expression (> or = 50%) was detected in 13 (93%) of the 14 G1 carcinomas, but in only 4 (44%) of the 9 G2/G3 carcinomas (p<0.05).


CONCLUSIONS
The Topo II alpha index and the results of in vitro chemosensitivity testing may be of assistance in selecting the appropriate chemotherapeutic drugs against gynecologic malignancies based on their histological type and differentiation, along with MRP expression.
Koshiyama
M
M
Department of Obstetrics and Gynecology, Teri Hospital, Nara, Japan. koshiya@mb.infoweb.ne.jp
Fujii
H
H
Kinezaki
M
M
Morita
Y
Y
Nanno
H
H
Yoshida
M
M
D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018269:Carcinoma, Endometrioid / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002454:Cell Differentiation; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D012074:Remission Induction; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002945:Cisplatin; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D005047:Etoposide; D008565:Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins