P-glycoprotein as an intermediate end point of drug resistance to neoadjuvant chemotherapy in locally advanced gastric cancer.
The expression of p-glycoprotein (p-gp) was evaluated in pre- and post-chemotherapy states after the administration of adriamycin-based chemotherapy in 24 gastric cancer patients. Among them, group A was composed of twelve patients who relapsed after surgery plus adjuvant chemotherapy and group B was composed of another twelve patients who received neoadjuvant chemotherapy plus surgery. Pre-chemotherapy p-gp was evaluated in 18 out of 24 patients (6 patients had no pre-chemotherapy paraffin blocks) and post-chemotherapy p-gp was evaluated from all 24 patients. Pre- and post-chemotherapy p-gp was expressed in 5 of 18 patients (27.8%), and 9 of 24 patients (37.5%), respectively, with immunohistochemical stain using monoclonal antibody JSB-1. No differences of disease-free survivals were observed in Group A based on post-chemotherapy p-gp expression from relapsed lesions. In Group B, there was a higher relapse rate (p = 0.04) and a lower one-year disease-free survival rate (p = 0.04) in post-chemotherapy p-gp positive patients when adjuvant treatment was done with the same regimen as neoadjuvant chemotherapy. In all patients studied, post-chemotherapy p-gp expression correlated with a higher systemic recurrence (p = 0.04). These data suggest that p-gp can be induced by an adriamycin-based chemotherapy in gastric cancer. Thus, we suggest that the prognosis of gastric cancer may be poor if a multidrug resistance (MDR)-related regimen is used in the presence of p-gp after neoadjuvant chemotherapy with an adriamycin-based regimen, even if the initial response is good.
Chung
H C
HC
Department of Internal Medicine, General Surgery, Yonsei University College of Medicine, Seoul, Korea.
Gong
S J
SJ
Yoo
N C
NC
Noh
S H
SH
Kim
J H
JH
Roh
J K
JK
Min
J S
JS
Kim
B S
BS
Lee
K B
KB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D016019:Survival Analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin