CORRELATION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 MESSENGER-RNA WITH PROTEIN EXPRESSION IN PRIMARY BREAST-CANCER TISSUES - DETECTION OF HIGHER LEVELS IN TUMORS WITH POOR PROGNOSTIC FEATURES

Background: The insulin-like growth factor (IGF)-binding proteins (IGF BPs) regulate the actions of the IGFs by influencing interactions betw een the IGFs and the IGF receptors. IGFBP-3, one of the six known spec ies of IGFBPs, is the predominant IGFBP in serum and is expressed by b reast cancer cells. Compared with estrogen receptor (ER)-positive samp les, ER-negative breast cancer cell lines and tumors express higher le vels of IGFBP-3. Therefore, expression of IGFBP-3 may be relevant in b reast cancer biology, although it is unknown whether IGFBP-3 levels co rrelate with other breast cancer prognostic factors besides ER status. It is also not known how different methods used to measure IGFBP-3 in breast cancer correlate. Purpose: We measured IGFBP-3 messenger RNA ( mRNA) and protein levels in breast tumors by different methods to test how these methods compare and to investigate the relationship between IGFBP-3 and breast cancer prognostic factors. Methods: We analyzed 40 human breast tumors and examined IGFBP-3 expression by ligand blot an alysis, immunoblot analysis, immunoradiometric assay (IRMA), and ribon uclease protection assay. Another set of 40 breast tumors, selected ac cording to ER and progesterone receptor (PR) status, S phase, and ploi dy, was analyzed by IRMA. Results: In 26 (65%) of 40 samples in which RNA could be isolated, IGFBP-3 mRNA levels correlated with IGFBP-3 lev els measured by IRMA (two-sided; P =.0001) but not with IGFBP-3 levels measured by ligand blot or immunoblot. Protein levels were highly cor related among all protein assays. Because the IRMA was more sensitive and accurate than the ligand blot and immunoblot assays, we used IRMA to examine IGFBP-3 levels in an additional 20 primary breast tumors wi th poor prognostic features (ER and PR negativity, high S phase, and a neuploidy) and in 20 tumors with good prognostic factors (opposite fea tures). IGFBP-3 levels were threefold higher in tumors with poor progn ostic features (mean +/- standard deviation = 32.8 +/- 25.2 versus 11. 8 +/- 9.7 ng/mg; two-sided; P =.003). Conclusions: These findings sugg est that in human breast cancer, IGFBP-3 mRNA and protein levels are c orrelated and higher levels of IGFBP-3 are detectable in tumors with p oor prognostic features. Implications: IGFBP-3 may be involved in the regulation of breast cancer cell growth.