Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins.
OBJECTIVE
Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST). Multidrug resistance (MDR) has been associated with the expression of P-glycoprotein (P-gp), multidrug resistance protein (MRP(1)), and lung resistance protein (LRP). The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters.


METHODS
Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST. Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP(1), LRP, and c-kit.


RESULTS
Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P: <.05). Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients. LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P: <.001). P-gp and MRP(1) expression was more pronounced in GIST than in LMS (P: <.05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP(1) expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST. LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients.


CONCLUSIONS
LMS patients have a better survival than GIST patients, and the metastatic pattern is different. Expression of MDR proteins in LMS is less pronounced than in GIST.
Plaat
B E
BE
Department of Pathology, University Hospital Groningen, The Netherlands. b.e.ch.plaat@kno.azg.nl
Hollema
H
H
Molenaar
W M
WM
Torn Broers
G H
GH
Pijpe
J
J
Mastik
M F
MF
Hoekstra
H J
HJ
van den Berg
E
E
Scheper
R J
RJ
van der Graaf
W T
WT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis* / Q000378:metabolism; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein