Prognostic value of cytosolyc cathepsin D content in resectable gastric cancer

Background and Aims: Cathepsin D (Cath-D) is an aspartyl protease involved in protein catabolism and tissue remodelling. In the present article, we evaluate the tumor content of Cath-D in resectable gastric carcinomas and its relation with clinical and pathological parameters, as well as its prognostic significance. Method: This prospective study included a series of 60 patients with primary gastric adenocarcinoma, who first underwent a complete surgical resection of their tumors and then were evaluated for disease recurrence and survival status during a mean follow-up period of 41.5 months. Cath D was measured in cytosolic samples using an immune-radiometric assay which determined the total amount of Cath-D (52K, 48K, and 34K). Results: The tumor content of Cath-D ranged from 4 to 247 pmol/mg protein and from 6.4 to 97.7 pmol/mg protein in adjacent non-neoplastic mucosa samples. Cytosolic Cath-D levels were significantly higher in neoplastic tissues (P < 0.001). Statistical analysis also demonstrated that younger patients showed lower Cath-D tumor levels than older ones. Likewise, patients with lower tumor levels of Cath-D had better survival than those with intermediate or high Cath-D tumor content (P = 0.002). This finding showed an independent prognostic value on survival (P = 0.02). Conclusions: The present study demonstrates the presence of higher Cath-D content in gastric carcinomas than in adjacent non-neoplastic mucosa, and that high intratumor Cath-D levels indentify a subgroup of resectable gastric cancer patients with a high probability of relapse as well as worse (C) 2004 Wiley-Liss, Inc.