Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.
BACKGROUND
Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes.


OBJECTIVE
To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer.


METHODS
Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients.


METHODS
Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies.


RESULTS
CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB.


CONCLUSIONS
Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.
Farinati
F
F
Cattedra Malattie Apparato Digerente, Istituto di Medicina Interna, Policlinico Universitario, Padova, Italy.
Herszényi
L
L
Plebani
M
M
Carraro
P
P
De Paoli
M
M
Cardin
R
R
Roveroni
G
G
Rugge
M
M
Nitti
D
D
Grigioni
W F
WF
D'Errico
A
A
Naccarato
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002401:Cathepsin B / Q000032:analysis*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D005757:Gastritis, Atrophic / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D013274:Stomach Neoplasms / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D017395:Plasminogen Activator Inhibitor 1; D002403:Cathepsins; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L