[Expression and prognostic value of the drug resistance markers P-gp, Mrp1, Mrp2, and Lrp in ovarian carcinoma].
BACKGROUND
Intrinsic and/or acquired chemoresistance is the major obstacle to overcome in the treatment of patients with ovarian carcinoma. The aim of the present study was to investigate the prognostic value of drug resistance associated proteins P-glycoprotein (P-gp), multidrug resistance related protein (Mrp1), canalicular multispecific organic anion trans-porter (c-MOAT or Mrp2) and lung resistance protein (Lrp) in ovarian carcinoma.


METHODS
Expression of P-gp, Mrp1, Mrp2 and Lrp was determined by immunohistochemistry of frozen tissue sections of 115 ovarian carcinoma patients and associated to clinico-pathological factors, response to chemotherapy and (progression free) survival.


RESULTS
Expression of P-gp was observed in 20 out of 115 (17%), Mrp1 in 51 out of 115 (44%), Mrp2 in 19 out of 115 (16%) and Lrp in 85 out 115 (74%) tumors. Expression of Mrp1 was related to Mrp2 (p < 0.0001) and P-gp (p < 0.001) expression, while Lrp expression was more frequently observed in patients with stage I/II versus stage III/IV tumors (p < 0.01), grade I/II versus III tumors (p < 0.05) and residual tumor < 2 cm versus > 2 cm after laparotomy (p < 0.05). Lower stage (p < 0.001), small residual tumor after first laparotomy (p < 0.001) and lower differentiation grade (p < 0.05) were related to longer (progression free) survival. P-gp, Mrp1, Mrp2, and Lrp expression was neither related to response to first line chemotherapy (59 evaluable patients) nor to (progression free) survival (all patients). On multivariate analysis only stage and residual tumor after first laparotomy were independent prognostic factors for (progression free) survival.


CONCLUSIONS
In ovarian carcinoma Mrp1 expression is associated with Mrp2 and P-gp expression, while Lrp expression is associated with favorable clinicopathological characteristics. Assessment of P-gp, Mrp1, Mrp2 or Lrp does not allow prediction of response to chemotherapy or (progression free) survival in ovarian carcinoma.
Katsaros
D
D
Dipartimento di Discipline Ginecologiche ed Ostetriche, Università degli Studi, Torino. dhocc@tin.it
Fracchioli
S
S
Arts
H J
HJ
de Vries
E G
EG
Danese
S
S
Richiardi
G
G
Arisio
R
R
Gordini
G
G
Van der Zee
A G
AG
Suurmeijer
A J
AJ
Massobrio
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1