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 closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma.


METHODS
In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1-285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (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). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only.


CONCLUSIONS
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 intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.
Ikeguchi
M
M
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan. surgery1@grape.med.tottori-u.ac.jp
Fukuda
K
K
Oka
S
S
Yamaguchi
K
K
Hisamitsu
K
K
Tsujitani
S
S
Sakatani
T
T
Ueda
T
T
Kaibara
N
N
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002402:Cathepsin D / Q000032:analysis* / Q000276:immunology; D003593:Cytoplasm / Q000737:chemistry; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D002402:Cathepsin D