Multidrug resistance proteins in primary and metastatic soft-tissue sarcomas: down-regulation of P-glycoprotein during metastatic progression.
BACKGROUND
Chemotherapy sensitivity of soft-tissue sarcomas (STS) is limited, which may be due to multidrug resistance (MDR). MDR is associated with expression of P-glycoprotein (P-gp), Multidrug Resistance-associated Protein 1 (MRP1) and Lung Resistance-related Protein (LRP). It is unknown whether in STS metastasis is more resistant than the primary counterpart.


METHODS
In 35 chemonaive STS and their metastases (86% chemonaive), MDR proteins were immunohistochemically assessed. Eleven metastases presented synchronously, 24 metachronously. Expression was scored positive (>5% positive tumour cells) or negative.


RESULTS
P-gp was positive in 31/34 primaries (91%), versus 22/32 metastases (69%) (p=0.005). This difference was significant for metachronous metastases (p=0.008). MRP1 was positive in 18/32 primaries (56%) and 22/33 metastases (67%). MRP1 was more expressed in synchronous metastases than primaries (p=0.047), but for the overall group this significance disappeared. LRP expression did not differ: 27/34 primaries (80%), versus 28/34 metastases (82%).


CONCLUSIONS
P-gp, MRP1, LRP expression in the primary tumours was high. Metastatic progression did not coincide with MDR-protein up-regulation.
Komdeur
Rudy
R
Department of Surgical Oncology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Molenaar
Willemina M
WM
Zwart
Nynke
N
Hoekstra
Harald J
HJ
van den Berg
Eva
E
van der Graaf
Winette T A
WT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D006801:Humans; D008207:Lymphatic Metastasis; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D015854:Up-Regulation; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1