Immunostained cathepsins B and L correlate with depth of invasion and different metastatic pathways in early stage gastric carcinoma

BACKGROUND. With the recent development of minimal treatment for early stag e gastric carcinoma, identifying specific indicators of the metastatic pote ntial of primary tumors has become more important. Cathepsin B and cathepsi n L, both lysosomal cysteine proteases, degrade the extracellular matrix du ring tumor progression. Although many studies have shown their relation to human cancer progression, little is known about their roles in the early st age. The clinicopathologic significance of cathepsins was therefore studied in early stage gastric carcinoma. METHODS. Expression of both cathepsins was studied immunohistochemically in 51 tissue specimens from gastric carcinomas that invaded the submucosal la yer or muscularis propria. The relation between their expression and clinic opathologic factors was analyzed. RESULTS. Both cathepsins were expressed at higher levels in tumors that inv aded the muscularis propria than in those within the submucosa (P < 0.05). In addition, tumors with lymphatic invasion showed higher cathepsin B expre ssion than those without it (P < 0.05), whereas tumors with Venous invasion showed higher cathepsin L expression than those without it (P < 0.05). No other clinicopathologic factors correlated with expression of either cathep sin. CONCLUSIONS. Tumors with overexpression of cathepsins have powerful potenti al for invasiveness in the early stage of gastric carcinoma. Moreover, the authors hypothesize that cathepsins may be one of the determinants of the m etastatic route. To the authors' knowledge, this is the first report on spe cific proteases concerning the mode of metastasis, and the results of this study suggest that therapeutic strategies for early stage gastric carcinoma might need to be changed according to the status of cathepsins. (C) 2000 A merican Cancer Society.