ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma.
OBJECTIVE
The purpose of this study is to attempt to characterize patients with unfavorable clinical outcome by the relative mRNA levels of ABC transporter expression in their tumor samples and to examine whether relative mRNA levels of each of the ABC transporters can be a useful predictor of progression-free survival in advanced ovarian carcinoma.


METHODS
We examined tumor samples taken from 30 patients with primary serous papillary adenocarcinoma of the ovary for the expression of MDR1 and MRP1, MRP2, and MRP3 mRNA by using real-time reverse transcription-PCR, and we evaluated its correlation with clinical outcome. All 30 patients were divided into three groups according to clinical outcome after debulking surgery and platinum-based chemotherapy: 8 patients were classified into the unfavorable group; 11 were classified into the favorable group; and 11 were classified into intermediate group.


RESULTS
The relative mRNA levels of MRP1 and MRP3 were significantly different among the three groups, and the mRNA levels of MRP1 and MRP3 in the unfavorable group were significantly higher than those in the favorable group by multiple comparison. The relative mRNA levels of MRP1 expression were significantly correlated with those of MRP3 expression. In the 30 patients with serous papillary adenocarcinoma, univariate and multivariate analysis demonstrated that the high relative mRNA levels of MRP1 expression were significantly correlated with a short period of progression-free survival.


CONCLUSIONS
In patients with advanced ovarian serous papillary adenocarcinoma, these results suggest that patients with an unfavorable clinical outcome are characterized by increased levels of coordinated MRP1 and MRP3 mRNA expression in their tumor samples. Furthermore, a higher level of MRP1 mRNA expression can be a candidate for a useful predictor of a shorter period of progression-free survival.
Ohishi
Yoshihiro
Y
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Oda
Yoshinao
Y
Uchiumi
Takeshi
T
Kobayashi
Hiroaki
H
Hirakawa
Toshio
T
Miyamoto
Shingo
S
Kinukawa
Naoko
N
Nakano
Hitoo
H
Kuwano
Michihiko
M
Tsuneyoshi
Masazumi
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D026901:Membrane Transport Proteins; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017931:DNA Primers; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000715087:ABCC2 protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1