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Overexpression of Epidermal Growth Factor and Hepatocyte Growth Factor Receptors in a Proportion of Gastrinomas Correlates with Aggressive Growth and Lower Curability

Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases [P. L. P., M. I., S. U. G., J. S., R. T. J.] and Hematopathology Section, Laboratory of Pathology, National Cancer Institute [M. R.], NIH, Bethesda, Maryland 20892

Purpose: Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear.

Experimental Design: To address this question, we analyzed the extent of EGFR and HGFR expression in gastrinomas from 38 patients with Zollinger-Ellison syndrome and correlated it with clinical and tumor characteristics. EGFR (n = 38) and HGFR (n = 22) mRNA levels were determined by competitive PCR, and immunohistochemistry was performed on a subset.

Results: In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present. Low levels of EGFR protein expression were detected in 40% of gastrinomas and HGFR protein expression in 90%. EGFR mRNA expression varied by 1050-fold and HGFR by 375-fold. Eighteen percent of gastrinomas overexpressed EGFR mRNA and 14% overexpressed HGFR mRNA, compared with normal pancreas. Maximal EGFR and HGFR mRNA levels were 4- and 1.2-fold increased and correlated with the presence of liver metastases (P = 0.034) and decreased long-term curability (P = 0.027) but not tumor location, size, or tumor functional characteristics.

Conclusions: These above results indicate that EGFR and HGFR mRNA are universally expressed in gastrinomas. Furthermore, each is overexpressed in a minority (15–20%) of the gastrinomas, and the overexpression correlates with aggressive growth and lower curability.

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