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Connective Tissue Oncology Society
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EXPRESSION oF P-gp, MRP1 AND LRP IN SOFT TISSUE SARCOMAS

Van der Graaf WTA, Plaat BEC, Hollema H, Hoekstra HJ, Mastik MF, Van den Berg E, Molenaar WM. University Hospital and University of Groningen, PO BOX 30.001, 9700 RB The Netherlands

Introduction: Differences in response to chemotherapy are observed between various types of soft tissue sarcomas (STS), which might be related to the presence of multidrug resistance (MDR). MDR has been associated with the overexpression of P-glycoprotein (P-gp), the multidrug resistance related protein-1 (MRP1), and the lung resistance protein (LRP). Therefore, the expression of P-gp, MRP1 and LRP with respect to histological type, tumor grade and mitotic activity was studied in 115 STS.

Material and methods: MDR-protein expression was immunohistochemically evaluated in paraffin embedded tumor material of chemotherapy naive STS. There were 23% grade I, 47% grade II and 30% grade III STS.

Results (table): Percentage of tumors with (co-) expression of the MDR proteins:

Diagnosis
FIBR
MFH
LPS
LMS
RMS
SYNS
MPNST
S-NOS
Other
all
n:
3
13
24
26
11
9
7
12
10
115
no MDR protein
  0%
  0%
 8%
 9%
 10%
11%
 0%
 0%
 0%
6%
P-gp
100%
100%
83%
32%
70%
89%
71%
63%
90%
71%
MRP1
 33%
  40%
33%
33%
18%
33%
71%
42%
 70%
39%
LRP
 33%
  92%
42%
88%
54%
55%
86%
92%
60%
70%
P-gp and MRP1
 33%
  40%
29%
13%
20%
33%
57%
36%
60%
32%
P-gp and LRP
 33%
  92%
33%
32%
40%
56%
57%
55%
50%
48%
MRP1 and LRP
  0%
  40%
17%
33%
  9%
11%
57%
42%
40%
48%
all 3 MDR proteins
  0%
  40%
13%
13%
10%
11%
43%
37%
30%
21%

 

P-gp expression was most pronounced in MFH and synovial sarcomas and low in LMS. MRP1 was most expressed in MPNST and low in RMS. LRP was most expressed in MFH and sarcoma NOS and low in LPS. All MFHs expressed at least one MDR protein. No correlation was found between tumor grade or mitotic activity and the expresssion of P-gp, MRP1 or LRP. Co-expression was less frequently observed in grade I STS.

Conclusions: P-gp, MRP1 and LRP are expressed in the majority of STS, whereas co-expression is frequently found. Expression of P-gp, MRP1 and LRP varies between histological types and is not related to tumor grade. Supported by the Dutch Cancer Society (Koningin Wilhelmina Fonds) Grant 95-1085

 

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