Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma

Objective: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as clo sely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prog nostic significance of cathepsin D expression in gastric adenocarcinoma. Me thods: In a consecutive series of 478 patients with gastric carcinoma (medi an follow-up period: 93 months, range: 1-285 months), cathepsin D expressio n in tumors was quantitatively analyzed with immunohistochemistry using a m onoclonal antibody against cathepsin D (clone: 1C11). The percentage of cat hepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grade s (high, intermediate, and low) were used for the classification. Results: The mean CD index of 478 tumors was 12.8% (range: 0-100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Catheps in D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathep sin D expression in stromal cells was significantly higher in well-differen tiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorl y differentiated tumors (19.1%). Cathepsin D expression of stromal cells wa s significantly associated with the depth of tumor invasion in the intestin al type, in contrast to the diffuse type. Highly expressed cathepsin D in c ancer cells was associated with a poor prognosis in both types of carcinoma , but in stromal cells highly expressed cathepsin D was associated to a poo r prognosis in the intestinal type only. Conclusion: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intesti nal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression. Copyright (C) 2001 S. Karger AG, Basel .