Interrelationship between Transforming Growth Factor-α and Epidermal Growth Factor Receptor in Advanced Gastric Cancer

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Abstract
An immunohistochemical study for transforming growth factor-α (TGFα) and epidermal growth factor receptor (EGFR) was made with 167 primary tumors of advanced gastric cancer to demonstrate the potential existence of autocrine mechanism. TGFα stained positively in 87 (52%), and EGFR in 68 (41%) of the tumors. The authors classified the tumors into the following three groups: group 1 with neither TGFα nor EGFR staining positively (63 tumors); group 2 with either TGFα or EGFR staining positively (53 tumors); group 3 with both TGFα and EGFR staining positively (51 tumors). The incidence rates of mac-roscopically infiltrative tumors and large tumor measuring 6 cm or more in diameter were significantly higher for group 3 than for groups 1 and 2. The patients of group 3 had the poorest prognosis, with a 5-year survival rate of only 12%, while the 5-year survival rates were 45 and 36% for groups 1 and 2. There was a significant difference in survival between the patients of group 1 and those of group 3. Bromodeoxy uridine labeling indices were significantly higher in the tumors belonging to group 3 (median 15.8%) than in those of group 1 (median 10.8%). The results suggest that the autocrine mechanism between TGFα and EGFR may play an important role in the progression of gastric cancer, and that when such a mechanism becomes operative, prognosis may be poor.

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