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1999 Abstract: 3470 THE EPIDERMAL GROWTH FACTOR RECEPTOR FAMILY IS DIFFERENTIALLY EXPRESSED IN PAPILLA OF VATER AND PANCREATIC CANCER: CAUSE FOR DIFFERENT PROGNOSIS

Abstracts
1999 Digestive Disease Week

# 3470 THE EPIDERMAL GROWTH FACTOR RECEPTOR FAMILY IS DIFFERENTIALLY EXPRESSED IN PAPILLA OF VATER AND PANCREATIC CANCER: CAUSE FOR DIFFERENT PROGNOSIS
H Friess, L Wang, Z Zhu, M E Martignoni, R Gerber, M Schroder, A Zimmermann, Univ of Bern, Inselspital, Bern Switzerland; M Korc, Univ of CA, Irvine, Irvine, CA; M W Buchler, Univ of Bern, Inselspital, Bern Switzerland

Cancer of the Papilla of Vater (papCa) has a much better prognosis than pancreatic cancer (pancCa). It is believed that this results from earlier symptoms and thereby earlier diagnosis. However, it is also possible that the biological growth behavior and genetic alterations in these tumors are different and that these changes influence the prognosis. In the present study, we compared the expression of the EGF receptor (EGFR), c-erbB2 and c-erbB3 in papCa and pancCa to evaluate whether differences in these genes may account for differences in the growth behavior of these tumors. Patients: PapCa tissue samples were obtained from 24 patients and PancCa tissue samples were obtained from 80 patients. 17 normal papilla of Vater tissue samples and 24 normal pancreatic tissues were obtained from healthy organ donors. Methods: EGFR, c-erbB2, and c-erbB3 mRNA expression were analyzed by Northern blot analysis and by in situ hybridization. In addition, immunohistochemistry using specific antibodies was used to localize the respective proteins. Results: By Northern blot analysis, EGFR and c-erbB2 mRNA expression were comparable, whereas c-erbB3 mRNA levels were significantly lower in papCa compared with the normal papilla. In contrast, pancreatic cancer samples exhibited enhanced mRNA expression of EGFR (4-fold), c-erbB2 (2.5-fold) and c-erbB3 (5.2-fold) compared with normal controls. In situ hybridization confirmed the Northern blot results and showed that mRNA expression was mainly restricted to the cancer cells. Immunohistochemical staining revealed comparable staining scores for EGFR in papCa (1.2±0.2) and the normal papilla (1.4±0.4). In contrast, lower staining scores in papCa samples in comparison with the normal papilla were present for c-erbB2 (2.7±0.4 vs. 3.9±0.5) and c-erbB3 (2.8±0.4 vs. 3.8±0.5). In pancreatic cancer, EGFR, c-erbB2 and c-erbB3 immunostaining scores were significantly higher in 60%, 49% and 57% of samples, respectively, compared with the normal controls. Conclusion: In papCa the expression of EGFR, c-erbB2 and c-erbB-3 is similar or lower compared with normal controls. In contrast, in pancCa, these growth factors are frequently overexpressed. These data strongly support the hypothesis that biological differences exist between pancreatic and papilla of Vater cancer and that these molecular differences may account for the better prognosis of papCa patients.

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