Immunohistochemical metallothionein expression in hepatocellular carcinoma: relation to tumor progression and chemoresistance to platinum agents.
BACKGROUND
Metallothionein (MT), which is known to detoxify heavy metal ions, is considered to serve as a mechanism of resistance to platinum complex compounds. In the present study, MT expression in hepatocellular carcinoma (HCC) was immunohistologically investigated to clarify its relationship to clinical background factors and responsiveness to anticancer drugs.


METHODS
Specimens from 117 patients with HCC were immunohistologically studied, using a monoclonal anti-MT antibody. the percentage of MT-positive HCC (MT ratio) cells was determined, to evaluate the extent of staining with anti-MT antibody. Staining with an MT ratio of more than 50% was categorized as diffusely positive; an MT ratio of 5% to less than 50% was focally positive; and an MT ratio of less than 5% was negative. Twenty-two patients received repeated arterial infusion chemotherapy with carboplatin (CBDCA), a platinum-containing compound, and the MT expression was analyzed in relation to their chemotherapeutic response.


RESULTS
The ratio of MT-positive cells in HCC decreased with the degree of histological differentiation and also decreased with higher tumor stage. In patients treated with CBDCA, the ratio of MT-positive cells in responders was significantly lower than that in non-responders.


CONCLUSIONS
MT expression decreases with the degree of histological differentiation and decreases with increasing tumor stage in HCC. In addition, MT expression may lower the antitumor effect of CBDCA.
Endo
Tsunehiro
T
First Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Yoshikawa
Masaharu
M
Ebara
Masaaki
M
Kato
Kazuki
K
Sunaga
Masahiko
M
Fukuda
Hiroyuki
H
Hayasaka
Akira
A
Kondo
Fukuo
F
Sugiura
Nobuyuki
N
Saisho
Hiromitsu
H
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D008875:Middle Aged
D000970:Antineoplastic Agents; D008668:Metallothionein; D016190:Carboplatin