Role of metallothionein in Helicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy.
OBJECTIVE
Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy.


METHODS
Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years.


RESULTS
MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05).


CONCLUSIONS
The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.
Mitani
Toshifumi
T
Departments of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Shirasaka
Daisuke
D
Aoyama
Nobuo
N
Miki
Ikuya
I
Morita
Yoshinori
Y
Ikehara
Nobunao
N
Matsumoto
Yuko
Y
Okuno
Tatsuya
T
Toyoda
Masanori
M
Miyachi
Hideyuki
H
Yoshida
Shiei
S
Chayahara
Naoko
N
Hori
Junko
J
Tamura
Takao
T
Azuma
Takeshi
T
Kasuga
Masato
M
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000382:microbiology*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis / Q000502:physiology*; D013274:Stomach Neoplasms / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control
D000900:Anti-Bacterial Agents; D008668:Metallothionein