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.