EpCAM expression in metastasizing gastric carcinomas.

B142

EpCAM, a homophilic Ca2+-independent adhesion molecule, is expressed in various tissues, especially proliferating tissues or neoplasias show an increasing expression of EpCAM. Since it is found in large quantities on carcinomas, it seemed to be useful as novel therapeutic target for monoclonal and bispecific antibodies raised against the protein. Due to lack of data in gastric carcinomas, we investigated these tumors and their corresponding metastases. Therefore we evaluated the immunohistochemical reactivity of 104 gastric cancers, and their lymph node as well as distant metastases, using the mouse monoclonal antibody ESA by use of a scoring system. EpCAM overexpression was as previously defined. Most of the tumour cells showed distinct membraneous reactivity, while normal gastric epithelium as internal control was EpCAM negative. 104 cases presented with an overexpression in 65,39%, without significant correlation to tumour stage or grade (p=0,339), no significant difference to histological growth patterns (according to Lauren) was found (p=0,186). 46,15 % of 26 mucinous carcinomas showed an overexpression, without mucinous parts they had an overexpression of 68 %, resulting in highly significant differences (p = 0.039 - two tailed) in these two groups. 54 primary tumors with metastases were evaluated. 62.96 % of these primary tumours had an EpCAM overexpression. 52 cases with lymph node metastases revealed a positive correlation with high significance (Pearson, p < 0.05). The paired-samples T-test no significance was found (p = 0.283 - two tailed). Comparing primary tumors with distant metastases a proportional relationship between the values was found (Pearson). The t-test brought no significant differences (p = 0.120). Between the lymph node metastases and distant metastases a positive correlation could be seen (Pearson, p = 0.192), without significance in the t-test (p = 0.121). Our study shows an EpCAM overexpression already in early stages of gastric cancers and a significant correlation between the primary tumors and metastases. So it seems to be possible to conclude from the EpCAM evaluation in available tissue of the primum to its metastases, facilitating clinical use of EpCAM-based immunotherapies and provide higher efficiency in the fight against all kinds of metastasizing gastric carcinomas. Recently designed new bispecific monoclonal antibodies are exerting improved therapeutic effects through antibody-dependent cellular cytotoxicity or complement. Also promising results were described for experimental gene therapy using EpCAM-targeted adenoviral vectors in human gastric and oesophageal carcinomas.