Increased estrogen receptor and epidermal growth factor receptor gene product co-expression in surgically resected gastric adenocarcinomas.

Background: Evidence exists that estrogens influence the action of epidermal growth factor (EGF) and its receptor (EGF-R) at multiple levels. Estrogen and antiestrogen action on gastric and other gastrointestinal malignancies has been evaluated by several groups with conflicting results, and EGF-R has been implicated in the current growth factor-mediated models for gastric cancer progression.

Methods: ERs and EGF-Rs were detected immunohistochemically in a total of 53 advanced gastric carcinomas using monoclonal antibodies (mAbs) to human ERs and EGF-Rs.

Results: ERs were expressed in 30 (56%) and EGF-Rs in 20 (38%) of the gastric tumors. ER(+) gastric tumors were closely associated with the intestinal type (P < 0.01), whereas EGF-R(+) tumors were significantly correlated with poor differentiation status and ER(+) expression (P < 0.01). Of EGF-R(+) tumors, 85% were also ER(+). EGF-R and ER co-expression was demonstrated in 17 tumors (32% of the group). These cases were significantly corelated with poor differentiation and large tumor size upon resection (P < 0.05).

Conclusions: ER and EGF-R co-expression indicates that a functional interaction between estrogens and EGF may exist in gastric cancer and that when such an interaction becomes operative, it may lead to dedifferentiation and increased tumor growth.