Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer

Background and Objectives: Limited operations for early gastric cancer (EGC ) have been recommended based on data from lymph node (LN) metastasis detec ted by hematoxylin and eosin (HE) staining. Recently, the clinical importan ce of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro -LN metastasis detected by cytokeratin (CK) immunostaining. Also, the corre lation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated. Methods: A total of 5,949 LNs from 160 patients with EGC were stained by an ti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were staine d by CD. Results: The incidence of LN metastasis increased from 7.5% (12/160) by HE- staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro- LN metastasis increased according to the depth of tumor invasion (mucosal c ancer: 19% and submucosal cancer: 36.8%) and the size of tumors (less than or equal to1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and >2.1 cm: 31.7%). The CK-sta ining patterns were classified into the three subgroups (CK-negative, n = 1 16; single cell type, n = 27, and clustered type, n = 17). The occurrence o f cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P <0.0001). The mean pe rcentage of CD-positive cancer cells of primary tumors in clustered type (1 7.2%) was significantly higher than in single cell type (12.3%) and in CK-n egative (7.5%, P = 0.0036). Conclusions: The acidic protease CD may play an important role of cancer me tastasis in EGG. The limited operation without lymphadenectomy should be in dicated for EGC with CD-negative. (C) 2001 Wiley-Liss, Inc.