To search for reliable predictors for lymph node metastasis, we immunohistochemically analyzed surgically resected gastric cancer specimens that showed invasion of submucosa (sm) and muscularis propria (mp) of the tumor. The analysis investigated cathepsin D and Ki-67 expression in 136 specimens that were divided into an sm1/sm2 group and an sm3/mp group. In sm1/sm2 group, the incidence of lymph node metastases was significantly higher in tumors with high Ki-67 labeling index (LI) (44%) than in those with low Ki-67 LI (0%). In sm3/mp group, the incidence of lymph node metastases was significantly higher in cathepsin D-positive (56%) and high Ki-67 LI tumors (64%) than in cathepsin D-negative (33%) and low Ki-67 LI (33%). Combined analysis of cathesin D expression and Ki-67 LI correlated strongly with lymph node metastases. No lesions with cathepsin D-negative expression and low Ki-67 LI had lymph node metastases in either group. Cathepsin D and Ki-67 expression may be useful predictors for lymph node metastases in gastric cancer with sm and mp invasion. As predictors, they can identify lesions without lymph node metastases and indicate lesions not needing additional treatment after endoscopic mucosal resection and laparoscopic gastrectomy.

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