Insulin-like growth factor-1 receptor gene expression is associated with survival in breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression

Abstract

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. In a series of 325 primary invasive breast cancer patients, we performed a comprehensive analysis of IGF1R at the levels of gene copy number, mRNA expression and protein expression. The relationship between the IGF1R status and the clinicopathological characteristics and prognosis was evaluated. IGF1R mRNA levels not only correlated with protein expression, but also were significantly associated with several clinicopathological parameters and prognosis. Patients with low nuclear grade, negative axillary lymph nodes, positive hormone receptor, negative Her2, negative Ki67, and luminal subtype tumors showed higher expression levels of IGF1R mRNA, which was shown to be a significant univariate parameter for both relapse-free survival and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for BCSS. IGF1R protein expression showed an association with a prolonged BCSS in univariate analysis. In contrast, IGF1R gene copy number was not correlated with mRNA and protein expression, and harbored no prognostic value. When studied in the luminal tumor subtype groups, IGF1R mRNA level was still significantly associated with a better BCSS. Overall, our data indicated a correlation between IGF1R mRNA expression and protein expression in primary breast cancer. In particular, IGF1R mRNA expression appeared to be a good prognostic marker both in the entire cohort and in the luminal subtype group. These data may serve as background information for IGF1R-targeted therapy.

IGF1R Protein Expression Is Not Associated with Differential Benefit to Concurrent Trastuzumab in Early-Stage HER2+ Breast Cancer from the North Central Cancer Treatment Group (Alliance) Adjuvant Trastuzumab Trial N9831

“…A study using a rabbit polyclonal antibody (SC713) showed that in 429 patients with stage I–III HER2+ breast cancer, 26% demonstrated IGF1R expression (Allred Score ≥ 7) and only 9% of HER2-enriched tumors had IGF1R expression (Allred score ≥ 7)(47). A study that utilized the same polyclonal antibody as our study (directed against the β subunit of IGF1R) showed that 65% of 297 unselected breast cancers did not have IGF1R protein expression and 3% of the cases had 3+ staining(39). This same antibody detected membrane IGF1R (when exceeded cytoplasmic staining) in 13.8% of 160 HER2+ breast cancers(25).…”

“…However, other radioimmunoassay studies have reported IGF1R as a favorable prognostic factor(41, 43) and although IGF1R levels were ten-fold higher in breast cancer than in normal breast, IGF1R levels were higher in a low-risk breast cancer group(44). Recent univariate analyses demonstrated that both mRNA levels and protein expression were associated with favorable prognosis, a longer breast cancer–specific survival (BCSS), but in the HER2 subtype, IGF1R protein was not significantly associated with BCSS or relapse-free survival(39). The prognostic significance of IGF1R expression may be then dependent on the molecular subtype of breast cancer.…”

Expression of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor 1 Receptor is Associated with the Favorable Clinicopathologic Parameters in Small Intestinal Carcinomas

“…However, its prognostic value is controversial depending on the sites of carcinoma [4,17,18,19,20,21,22]. Many reports suggested that IGF1R expression correlated with poor survival in breast cancer [18,23,24]. In contrast, Fu et al [23] described that IGF1R mRNA expression was significantly higher in patients with favorable clinicopathologic parameters.…”

“…Many reports suggested that IGF1R expression correlated with poor survival in breast cancer [18,23,24]. In contrast, Fu et al [23] described that IGF1R mRNA expression was significantly higher in patients with favorable clinicopathologic parameters. In gallbladder cancer, tumors with less than 50% of IGF1R immunoreactions showed a significantly worse prognosis [19].…”

Insulin and IGF-1 in breast cancer patients are associated with tumor cell proliferation (Ki67) in their breast tumors

“…A positive energy balance over time may promote breast cancer growth (1)(2)(3)(4)(5)(6). Potential mechanisms linking a positive energy balance to breast cancer risk and prognosis include elevated levels of circulating or tissue estrogens, insulin, insulin-like growth factor-1 (IGF-1) and low-grade chronic inflammation, as these factors are known to promote cell growth and inhibit apoptosis (1;2;2;3;3;5;7).…”