INCREASED EXPRESSION OF ERBB3 IN COLORECTAL-CANCER IS ASSOCIATED WITHCONCOMITANT INCREASE IN THE LEVEL OF ERBB2

ErbB3 is a transmembrane signaling molecule that shares close structur al homology with epidermal growth factor receptor (EGFR), erbB2, and e rbB4. They have all been implicated in cell transformation and tumor p athogenesis, but very little is known about the role of erbB3 in norma l colon and colorectal cancer. Therefore, in the current study, we det ermined whether erbB3 is found in normal human colon and whether its e xpression is altered in colorectal cancer. Because of some evidence th at erbB3 might interact with erbB2 and EGER, respectively, by heterodi merization, we also included erbB2 and EGFR analysis with special rega rd to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 an d erbB2 immunostaining, predominantly in surface epithelial cells. EGF R immunoreactivity in normal colon varied from weak to strong. In cont rast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderat e to strong immunoreactivity for erbB3 and erbB2, respectively, was pr esent in most epithelial cancer cells. A concomitant erbB3 and erbB2 i mmunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis s howed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respect ively, were calculated in the cancerous tissues. Eighty-five percent o f cancers with erbB3 mRNA overexpression showed an increase in erbB2 m RNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, ho wever, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increase d erbB2 and erbB3 expression in both Northern blots and immunohistoche mical analysis suggests a co-overexpression of erbB2 and erbB3 and mig ht support the hypothesis that these two growth factor receptors act t ogether by heterodimer formation. Copyright (C) 1998 by W.B. Saunders Company.