IGF-II MESSENGER-RNA AND PROTEIN ARE EXPRESSED IN THE STROMA OF INVASIVE BREAST CANCERS - AN IN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRYSTUDY

Insulin-like growth factor-II (IGF-II) is a potent mitogen for a varie ty of cell types and is considered an important regulator of breast ca ncer growth. In this study, we analyzed IGF-II mRNA and protein expres sion in a series of 80 cases of invasive breast cancer. Seventy-five c ases produced informative results for IGF-II mRNA expression, and were scored on an arbitrary scale. Two cases (2.6%) had no significant IGF -II mRNA expression. 35 cases (46.7%) expressed low levels of IGF-II m RNA, 20 cases (26.7%) moderate IGF-II mRNA, while 18 (24%) expressed h igh levels of IGF-II message. Generally, IGF-II mRNA was expressed in the smooth muscle walls of blood vessels and ducts, as well as in the stroma tightly adjacent to and surrounding tumor epithelium. IGF-II mR NA content was also directly related to the amount of the stroma withi n the tumor (p<0.05). In 10 cases (13.3%) IGF-II mRNA was detected in the stroma of normal lobules. Fifty-six out of 75 were positive for IG F-II immunostaining. Again, protein staining was generally observed in the smooth muscle of both blood vessels and ducts, as well as in the stroma surrounding tumor epithelium. In normal lobules and ducts the I GF-II protein was detected in the myoepithelium. Unequivocal IGF-II pr otein staining was seen in tumor epithelium in only three cases. The r esults of our study demonstrate that, in breast cancer, IGF-II mRNA is expressed in the smooth muscle and stromal components in the majority of invasive breast cancers. IGF-II expression correlates positively w ith the amount of stromal tissue present within a tumor. This suggests that IGF-II may have an important growth regulatory effect on breast tumor epithelium through paracrine pathways.