Background: By transactivation, phosphorylated insulin growth factor receptor I (IGF-1R) can activate epidermal growth factor receptor (EGFR). MMP-7, produced by colorectal cancer cells, also can activate IGF-1R by degrading IGFBP-3 and releasing IGF-I. Results: Expression of activated IGF-1R and MMP-7 was observed in 51 and 49% of patients, respectively. Coexpression of MMP-7 and pIGF-1R (double positivity, DP) was observed in 28 patients (25%). There was no association between KRAS or BRAF mutational status and DP (p = 0.52). Patients with DP responded more poorly to first-line chemotherapy (p = 0.005) and to anti-EGFR treatment (p = 0.01) than non-DP patients. In wild type (WT) KRAS patients, those with DP have poorer PFS (2.7 vs. 3.5 months, p = 0.036; HR 1.98, 95% CI 1.05-3.75) and OS (6.4 vs. 8.6 months, p = 0.010; HR 2.33, 95% CI 1.23-4.43) in the adjusted multivariate analysis. Methods: A cohort of patients with advanced colorectal cancer (CRC), under second-or third-line treatment with cetuximab or panitumumab, was tested using immunohistochemistry for expression of the activated form of IGF-1R (p-IGF-1R) and MMP-7. KRAS and BRAF mutation status was determined by sequencing and allelic discrimination analysis, respectively. Analyses were performed in primary CRC tumor samples or metastases, and the association of immunohistochemistry findings, mutational results and treatment outcomes was investigated in both univariate and multivariate analyses. Conclusions: Our study suggests that concomitant expression of MMP-7 and activation of p-IGF-1R (DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR. © 2011 Landes Bioscience.
Co-expression of matrix metalloproteinase-7 (MMP-7) and phosphorylated insulin growth factor receptor i (pIGF-1R) correlates with poor prognosis in patients with wild-type KRAS treated with cetuximab or panitumumab A GEMCAD study
RUBINI, Michele;
2011
Abstract
Background: By transactivation, phosphorylated insulin growth factor receptor I (IGF-1R) can activate epidermal growth factor receptor (EGFR). MMP-7, produced by colorectal cancer cells, also can activate IGF-1R by degrading IGFBP-3 and releasing IGF-I. Results: Expression of activated IGF-1R and MMP-7 was observed in 51 and 49% of patients, respectively. Coexpression of MMP-7 and pIGF-1R (double positivity, DP) was observed in 28 patients (25%). There was no association between KRAS or BRAF mutational status and DP (p = 0.52). Patients with DP responded more poorly to first-line chemotherapy (p = 0.005) and to anti-EGFR treatment (p = 0.01) than non-DP patients. In wild type (WT) KRAS patients, those with DP have poorer PFS (2.7 vs. 3.5 months, p = 0.036; HR 1.98, 95% CI 1.05-3.75) and OS (6.4 vs. 8.6 months, p = 0.010; HR 2.33, 95% CI 1.23-4.43) in the adjusted multivariate analysis. Methods: A cohort of patients with advanced colorectal cancer (CRC), under second-or third-line treatment with cetuximab or panitumumab, was tested using immunohistochemistry for expression of the activated form of IGF-1R (p-IGF-1R) and MMP-7. KRAS and BRAF mutation status was determined by sequencing and allelic discrimination analysis, respectively. Analyses were performed in primary CRC tumor samples or metastases, and the association of immunohistochemistry findings, mutational results and treatment outcomes was investigated in both univariate and multivariate analyses. Conclusions: Our study suggests that concomitant expression of MMP-7 and activation of p-IGF-1R (DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR. © 2011 Landes Bioscience.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
