ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas.
The phenomenon of multidrug resistance (MDR) in various malignant neoplasms has been reported as being caused by one or multiple expressions of ATP-binding cassette (ABC) superfamily protein, including P-glycoprotein/multidrug resistance (MDR) 1 and the MDR protein (MRP) family. However, their expression levels and distribution within soft tissue sarcomas remain controversial. In 86 cases of surgically resected soft tissue sarcoma, intrinsic mRNA levels of MDR1, MRP1, MRP2 and MRP3 were assessed using a quantitative reverse transcriptase-PCR (RT-PCR) method. Moreover, immunohistochemical protein expressions of P-glycoprotein (P-gp), MRP1, MRP2, MRP3 and p53 protein were evaluated in concordant paraffin-embedded material. The mRNA expression and immunohistochemical expression of ABC superfamily transporters were compared to clinicopathologic parameters and proliferative activities as evaluated by the MIB-1-labeling index (LI). Among the various histologic types, malignant peripheral nerve sheath tumor (MPNST) showed significantly high levels of MDR1 (p=0.017) and MRP3 (p=0.0384) mRNA expression, compared to the other tumor types. When the immunohistochemical method was compared to the RT-PCR technique to assess ABC transported expression at the protein and mRNA levels, a significantly close relationship was found between the 2 methods (p<0.05). P-gp expression was significantly correlated with large tumor size (> or =5 cm, p=0.041) and high AJCC stage (stages III and IV) (p=0.0365). Furthermore, cases with nuclear expression of p53 revealed significantly higher levels of MDR1 mRNA expression, compared to those with negative immunoreaction for p53 (p=0.0328). Our results suggest that MDR1/P-gp expression may have an important role to play in tumor progression in the cases of soft tissue sarcoma, and p53 may be one of the active regulators of the MDR1 transcript. In addition, the high levels of both MDR1 and MRP3 mRNA expression in MPNST may help to explain the poor response of this tumor to anticancer-drugs.
Oda
Yoshinao
Y
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. oda@surgpath.med.kyushu-u.ac.jp
Saito
Tsuyoshi
T
Tateishi
Naomi
N
Ohishi
Yoshihiro
Y
Tamiya
Sadafumi
S
Yamamoto
Hidetaka
H
Yokoyama
Ryohei
R
Uchiumi
Takeshi
T
Iwamoto
Yukihide
Y
Kuwano
Michihiko
M
Tsuneyoshi
Masazumi
M
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters