Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma.
OBJECTIVE
To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC).


METHODS
The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups.


RESULTS
Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome.


CONCLUSIONS
The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.
Akimoto
Masahide
M
Department of Medicine and Clinical Oncology, School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba City, Chiba 260-0856, Japan. khikyoku@mb.infoweb.ne.jp
Yoshikawa
Masaharu
M
Ebara
Masaaki
M
Sato
Tsunenobu
T
Fukuda
Hiroyuki
H
Kondo
Fukuo
F
Saisho
Hiromitsu
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D015251:Epirubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008942:Mitoxantrone / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015251:Epirubicin; D016190:Carboplatin; D008942:Mitoxantrone