Expression of P-glycoprotein in epithelial ovarian cancer: evaluation as a marker of multidrug resistance.
The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein that mediates active cellular efflux of certain chemotherapeutic agents. P-Glycoprotein expression was evaluated in 98 frozen tumor specimens from 57 patients with epithelial ovarian cancer by the indirect immunoperoxidase technique with monoclonal antibodies C219 and JSB-1 used for detection. Tumor specimens were further characterized antigenically with a panel of monoclonal antibodies representing a variety of epithelial cell antigens. Included were 57 specimens from 33 previously untreated patients; 11 specimens were also available from eight patients in this group after chemotherapy. An additional 30 specimens were studied from 24 other patients after chemotherapy. In only four of the 57 patients with ovarian cancer (7%) did one or more of the specimens express P-glycoprotein. Two of these patients had tumors that were considered clinically drug resistant. No increase in P-glycoprotein expression was noted after exposure to chemotherapy, including the eight individuals for whom specimens were available both before and after treatment. Although drug resistance is a major problem in treatment of ovarian cancer, resistance to the drugs most active against these tumors probably occurs through a mechanism other than expression of the MDR1 gene product.
Rubin
S C
SC
Memorial Sloan-Kettering Cancer Center, New York, New York.
Finstad
C L
CL
Hoskins
W J
WJ
Saigo
P E
PE
Provencher
D M
DM
Federici
M G
MG
Hakes
T B
TB
Markman
M
M
Reichman
B S
BS
Lloyd
K O
KO
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011506:Proteins