Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with preoperative chemotherapy.
Our purpose was to determine the expression of the drug resistance factors multidrug resistance protein (MRP1), lung resistance protein (LRP) and P-glycoprotein (Pgp) in breast carcinoma patients treated with preoperative chemotherapy. We have studied the expression of these proteins in breast carcinomas by immunohistochemistry both prior (n = 80) and after (n = 68) preoperative chemotherapy and compared their expression with response to preoperative chemotherapy. In paired samples prior and after chemotherapy expression of drug resistance factors was significantly lower in prechemotherapy samples as compared with postchemotherapy specimens. This was observed for MRP1 (62% vs. 88%, P < 0.001), LRP (65% vs. 97%, P < 0.001) and Pgp (55% vs. 100%, P < 0.001). Prechemotherapy expression of MRP1 was more frequently observed in patients with distant metastases than in those without (50% vs. 8%, P = 0.02). No associations were observed between LRP expression and clinical parameters. Pgp expression was more frequently detected in lobular carcinomas than in ductal carcinomas (93% vs. 46%, P = 0.001) and in patients with positive lymph nodes than in patients with negative lymph nodes (65% vs. 31%, P = 0.008) but was independent of other clinical parameters. No significant associations were found between the prechemotherapy or postchemotherapy expression of either of these three proteins and response to preoperative chemotherapy. However, prechemotherapy MRP1 expression was significantly associated with shorter progression-free survival of the patients (P = 0.02), whereas no such associations were observed for either LRP or Pgp. In conclusion, preoperative chemotherapy increases the expression of MRP1, LRP and Pgp. Response to chemotherapy is not associated with pre- or postchemotherapy expression levels of these drug resistance proteins but time to progression may be influenced by prechemotherapy MRP1 expression.
Department of Pathology, University of Vienna, Vienna, Austria.
Margaretha
M
Rudas
Martin
M
Filipits
Susanne
S
Taucher
Thomas
T
Stranzl
Günther G
GG
Steger
Raimund
R
Jakesz
Robert
R
Pirker
Gudrun
G
Pohl
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; 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