Cathepsin B expression and its correlation with tumor-associated laminin and tumor progression in gastric cancer

Ashraf Khan, University of Massachusetts Medical School
Murli Krishna
Stephen P. Baker, University of Massachusetts Medical School
Rajwant Malhothra
Barbara F. Banner, University of Massachusetts Medical School

Document Type Article

Abstract

OBJECTIVE: Cathepsin B, a lysosomal cysteine proteinase, is associated with degradation of laminin. Its activity has been shown to be increased in gastric carcinomas. Laminin is one of the major components of basement membrane involved in cell-matrix interactions and tumor progression. The objectives of this study were to correlate cathepsin B expression in tumor cells with tumor-associated laminin and to further correlate the two with tumor progression.

DESIGN AND SETTING: Resected gastric carcinomas (n = 29) taken from the surgical pathology files of the University of Massachusetts Medical Center, Worcester, were immunostained with cathepsin B and laminin using the avidin-biotin complex technique. Statistical analysis was performed using the exact linear by linear association test and exact Kruskal-Wallis test. Kaplan-Meier curves were plotted, and survival analysis was performed using a nonparametric log-rank test.

RESULTS: Cathepsin B was expressed in 27 (93%) of 29 tumors (11 weak and 16 strong). Staining of tumor-associated laminin showed patterns ranging from almost continuous (n = 4) to moderately discontinuous (n = 11) and highly fragmented (n = 14). The degree of cathepsin B staining in tumor cells significantly correlated with the laminin distribution pattern (P = .0001). The association between increased cathepsin B, decreased laminin, and higher tumor stage was also significant.

CONCLUSIONS: Increased cathepsin B expression by tumor cells associated with decreased tumor-associated laminin may suggest a mechanism for local tumor progression and metastasis. Staining for cathepsin B and laminin may be of prognostic value in gastric carcinomas.