EXPRESSION OF EPIDERMAL GROWTH-FACTOR (EGF), MATRIX METALLOPROTEINASE-9 (MMP-9) AND PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) IN ESOPHAGEAL CANCER

Abstract

Expression of human epidermal growth factor (EGF) and matrix metalloproteinase-9 (MMP-9/gelatinase B) was examined immunohistochemically in 62 cases of surgically resected esophageal carcinomas, and the correlation between EGF expression and the proliferative activity of the tumors was studied by analysing the number of proliferating cell nuclear antigen (PCNA)-positive cells. Expression of EGF and MMP-9 was observed in 16 (38.1%) and 18 (42.9%) of the 42 superficial carcinomas and 8 (40%) and 14 (70%) of the 20 advanced carcinomas, respectively. The differences in the MMP-9 expression between the superficial carcinomas and the advanced carcinomas was significant (p<0.05). The synchronous expression of EGF and MMP-9 was observed in 15 (24.2%) of 62 carcinomas, i.e. 62.5% of the 24 EGF-positive tumors expressed MMP-9, but there was no statistically significant correlation between the expression of EGF and MMP-9. The relationships between EGF expression and tumor proliferative activity and prognostic factors were investigated. The PCNA grades were significantly higher in tumors with EGF-positive than those with EGF-negative expression (p<0.05) and the EGF expression showed a good correlation between the expression of MMP-9 and vascular invasion (p<0.01). The expression of MMP-9 was stronger in the advanced than the superficial carcinomas and there was a good correlation with vascular invasion (p<0.01). In a follow-up study of 55 patients, those with tumor that expressed MMP-9 or had a high PCNA grade showed a poor prognosis. Taken together, these observations suggest that both EGF and MMP-9 participate in the invasive phenotype in human esophageal carcinoma, but the expression of EGF is not directly related to the expression of MMP-9. Additional growth factors and cytokines may be involved in regulation of MMP-9 expression in this carcinoma.