INSULIN-LIKE GROWTH FACTOR-I RECEPTORS ARE OVEREXPRESSED AND PREDICT A LOW-RISK IN HUMAN BREAST-CANCER

IGF-I receptor (IGFR) content and its prognostic significance were eva luated in human breast cancer specimens using a sensitive and specific radioimmunoassay (V. Pezzino et al., Metabolism, 40: 861, 1991). The prognostic significance of IGFR expression was investigated by two dif ferent approaches: (a) detectable IGFR content was measured in 82% of specimens in a consecutive series of 184 human breast cancers and in 3 2% of 19 normal breast tissues. The average IGFR content in breast can cer was nearly 10-fold higher than the value observed in normal breast tissue (7.6. +/- 0.8 versus 0.8 +/- 0.1 ng/0.1 mg protein, mean +/- S EM; P < 0.001). IGFR content was positively correlated with estrogen ( ER) and insulin receptor content (r = 0.269 and 0.515, respectively, P earson correlation) but not with progesterone receptors (PR). No signi ficant correlation was observed between IGFR content and a variety of tumor parameters (tumor size, lymph node involvement, grade) and host characteristics (age, body mass index, menopausal status); (b) IGFR co ntent was measured in a noncontinuous series of 265 primary breast can cer specimens subdivided into 136 high-risk and 129 low-risk specimens on the basis of being either negative (ER-/PR-/aneuploid/high S-phase ) or positive (ER+/PR+/diploid/low S-phase) for four well-established prognostic factors. IGFR levels were significantly higher in the low-r isk group (6.4 +/- 0.4 ng/0.1 mg protein, mean +/- SEM) than in the hi gh-risk group (3.6 +/- 0.5; P < 0.0001, Wilcoxon sum rank test). In su mmary, our data indicate that there is an elevated IGFR content in mos t human breast cancers compared with normal breast tissue and that an elevated IGFR content is a favorable prognostic indicator.