Clinicopathological Significance of Cathepsin D Expression in Gastric Adenocarcinoma

Abstract

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. 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 intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.

Evaluation of Cathepsin D Immunostaining in Colorectal Epithelial Tumors

“…There was a strong correlation between high CD expression in carcinomas of the M and SM. These results support previous studies in gastric adenocarcinomas that found a significant association between CD expression and the depth grading of tumor invasion 15,16) In addition, a correlation between CD expression and prognosis was reported in oesophageal squamous cell carcinoma 1') and breast carcinoma 6.'.1s). However, until now a similar association in colorectal tumors has not been confirmed s-11~.…”

Expression of cathepsin D and galectin 3 in tubular carcinomas of the breast

“…Cathepsin D immunohistochemical expression has also been assessed in a variety of tumours, such as gastric adenocarcinomas (11), colorectal carcinomas (12), lung adenocarcinomas and breast carcinomas (13, 14, 25, 26). Particularly in the case of breast carcinomas, some authors have reported that stromal expression of cathepsin D, together with E‐cadherin and lack of estrogen receptors, is considered an important prognostic factor, especially in lymph node‐negative patients (27), is an indicator of prognosis and metastasis from an early stage (26), and is positively correlated with tumour grade.…”

Immunohistochemical Expression of Cathepsin D in Primary and Recurrent Squamous Cell Carcinoma

“…It has been shown that cathepsin D has a relation with prognostic parameters like advanced tumor stage, 9 poor malignancy grade, 9,26 development of clinical metastasis, 7,27 depth of tumor invasion, 28,29 and was also reported to have increased intensity of expression in the advancing front of the lesion. 13,30 These observations which link increased cathepsin D expression to parameters reflective of a poorer grade of carcinoma were similar to our findings.…”