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

Cancer. 2000 Aug 1;89(3):482-7.


Background: With the recent development of minimal treatment for early stage gastric carcinoma, identifying specific indicators of the metastatic potential of primary tumors has become more important. Cathepsin B and cathepsin L, both lysosomal cysteine proteases, degrade the extracellular matrix during tumor progression. Although many studies have shown their relation to human cancer progression, little is known about their roles in the early stage. 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 layer or muscularis propria. The relation between their expression and clinicopathologic factors was analyzed.

Results: Both cathepsins were expressed at higher levels in tumors that invaded the muscularis propria than in those within the submucosa (P < 0.05). In addition, tumors with lymphatic invasion showed higher cathepsin B expression 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 cathepsin.

Conclusions: Tumors with overexpression of cathepsins have powerful potential for invasiveness in the early stage of gastric carcinoma. Moreover, the authors hypothesize that cathepsins may be one of the determinants of the metastatic route. To the authors' knowledge, this is the first report on specific 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cathepsin B / metabolism*
  • Cathepsin L
  • Cathepsins / metabolism*
  • Cysteine Endopeptidases
  • Endopeptidases*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*


  • Cathepsins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L