Relationships among the expression of epidermal growth factor receptor, proliferating cell nuclear antigen labeling index, and lymph node metastasis in gastric cancer.

The expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and the labeling index of proliferating cell nuclear antigen (PCNA LI) were examined immunohistochemically in 288 gastric cancer patients, and the relationships between these results and the lymph node metastasis were studied. To investigate the relation between the expression of EGFR and PCNA LI, we divided the patients into the following three groups according to the immunohistochemical findings: group A, EGFR (+); group B, EGFR (-), and EGF(+) or TGF alpha(+); group C, EGFR(-), EGF(-) and TGF alpha(-). In the cancers invading submucosal or proper muscle layer, high-PCNA tumors (PCNA LI > or = 70) in both groups A and B had more frequent lymph node metastasis than in the intermediate-(40-69) and low- (< or = 39) PCNA tumors. In the cancers invading subserosal layer or further, the frequency of metastasis in group A was over 78% and was not related to the PCNA range. In group B, metastasis was more frequent in high- and intermediate-PCNA tumors (about 80%) than in low-PCNA tumors (44%). These results suggest that growth regulation by EGFR is related to lymph node metastasis in gastric cancer, and the higher the PCNA LI of cancer cells becomes, the more frequent the occurrence of lymph node metastasis.