Abstract P1-01-12: Prevalence of insulin-like growth factor-1 receptor (IGF1R) expression in circulating tumor cells (CTCs) of patients with early breast cancer and its association with E-cadherin expression and patient survival
Authors: S Agelaki, M Spiliotaki, M Kokotsaki, A Matikas, E-K Vetsika, V Georgoulias, D Mavroudis
Journal: Cancer Research (2017)

Abstract Background: Components of the IGF system are deregulated and IGF1R overexpression is common in breast cancer (BC). E-cadherin (E-CAD) has a prominent role in epithelial differentiation. We investigated the expression of IGF1R in CTCs from patients (pts) with BC and evaluated its correlation with E-CAD expression and survival. Methods: Cytospins of peripheral blood mononuclear cells (PBMCs), obtained from early (n=62) and metastatic (n=100) pts before adjuvant and 1st-line chemotherapy, respectively, were analysed. Cytospins were double or triple stained with anti-cytokeratin (CK) (A45-B/B3) and anti-IGF1R or with anti- CK, -IGF1R and -E-CAD antibodies, respectively, and evaluated by immunofluorescent microscopy (Ariol system). Results: CTCs were detected in 20 (32%) and 45 (45%) pts with early and metastatic BC, respectively. IGF1R(+) CTCs were more prominent in early (84% vs 64% of total CTCs, p=0.0007) and IGF1R(-) CTCs in metastatic disease (36% vs 16%, p=0.0001). Among early pts, 80% had exclusively IGF1R(+) CTCs, 20% had both IGF1R(+) and IGF1R(-) and none had exclusively IGF1R(-) CTCs. The respective values in metastatic pts were 42%, 33% and 25% (p=0.005). Early BC pts with exclusively IGF1R(+) CTCs had significantly higher DFS (p=0.0283) and OS (p=0.0016) compared to those with both subpopulations. Triple IF staining revealed that IGF1R(-)/E-CAD(-) CTCs prevailed in metastatic disease (54% vs 6% of total CTCs, p=0.0167). Among early pts, 67% had exclusively IGF1R(+)/E-CAD(+) CTCs, 33% also had IGF1R(-)/E-CAD(-) and none had exclusively IGF1R(-)/E-CAD(-) CTCs. The respective values in metastatic pts were 15%, 77% and 8%, (p=0.03). Among CTC(+) early BC pts with detectable CTCs on relapse, the median % of IGF1R(+)/E-CAD(+) CTCs/pt was reduced (59% vs 89%) whereas the median % of IGF1R(-)/E-CAD(-) CTCs/pt increased (41% vs 11%) on disease progression. Conclusions: IGF1R(+) CTCs are detected more frequently in early compared to metastatic BC. IGF1R and E-CAD are co-expressed at the single CTC-level and the progression from early to metastatic disease is accompanied by a loss of both proteins. These results suggest that IGF1R expression on CTCs contributes to a more differentiated and less invasive phenotype possibly through E-CAD. Accordingly, IGFIR expression in CTCs is associated with improved survival in early BC. Citation Format: Agelaki S, Spiliotaki M, Kokotsaki M, Matikas A, Vetsika E-K, Georgoulias V, Mavroudis D. Prevalence of insulin-like growth factor-1 receptor (IGF1R) expression in circulating tumor cells (CTCs) of patients with early breast cancer and its association with E-cadherin expression and patient survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-12.