A significant expression of IGFBP2 in infiltrating breast cancer compared to carcinoma in situ and benign lesions

LT Busund MD PhD, E Richardsen MD, R Busund MD PhD, T Ukkonen, T Bjoernsen, C Busch MD PhD, H Stalsberg MD PhD

Department of Pathology, University Hospital of Northern Norway N-9038 Breivika, Tromsø, Norway

Aim: Insulin-like growth factors (IGFs) and insulin-like growth factors binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Insulin-like growth factor binding protein 2 (IGFBP2), one of the six members of the IGFBP superfamily, acts as regulator of the IGFs in addition to pleiotropic effects in normal and neoplastic transformed tissue. Since IGFs has mitogenic effects on mammary epithelia, we have focused on localization of IGFBP2 in mammary tissues of different benign and malignant entities. Methods: We have employed an immunohistochemical approach to make correlations between the presence and intensity of IGFBP2 staining with tumor type and grade, as well as steroid hormone receptor status. The protein expression was measured by quantitative color video image analysis and semiquantitative evaluation, and the measurements correlated well (Spearman, p< 0.001). Results: By both methods, normal glandular cells and hyperplasia (Group I) did not express IGFBP2. Atypical hyperplasia showed a slightly increased cytoplasmic expression of IGFBP2 and carcinoma in situ showed a distinctive, membrane-associated and cytoplasmic expression (Group II). Infiltrating carcinoma strongly expressed cytoplasmic IGFBP2 (Group III). There were significant differences between group I and II, and between group II and III (Dunnet test). There were no significant differences between infiltrating lobular carcinomas and ductal carcinomas, or between grades I, II and III within these entities. There were no significant correlations between the level of IGFBP2 immunostaining and oestrogen receptor or progesterone receptor positivity within the malignant group (Mann-Whitney test). Conclusions: Neoplastic cells of infiltrating breast carcinoma express significantly more IGFBP2 than carcinoma in situ and benign lesions. There were no significant correlations between IGFBP2 expression and hormonereceptor status of the malignant entities.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 798 (Growth factors & signalling).