Immunohistochemical Detection of Fibroblast Growth Factor Receptor 3 in Human Breast Cancer: Correlation with Clinicopathological/Molecular Parameters and Prognosis

Kuroso, K; Imai, Yasuo; Kobayashi, Masashi; Yanagimoto, Kunio; Suzuki, Takahiro; Kojima, Masato; Ueda, Yoshihiko

doi:10.1159/000314346

Cited by 23 publications

(23 citation statements)

References 56 publications

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“…However, overexpression of FGFR3 has also been associated with poor differentiation and high nuclear grade in hepatocellular carcinoma (52). The overexpression of FGFR3 in invasive breast cancer was not significantly associated with specific clinicopathological characteristics, although it was suggested to be a candidate marker for a poor prognosis (53). In this study, the expression of FGFR3 was not significantly associated with clinicopathological findings or survival.…”

Section: Metastatic Lymph Nodescontrasting

confidence: 56%

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer

Murase

Inokuchi

Takagi

et al. 2014

Molecular and Clinical Oncology

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Abstract. The overexpression of fibroblast growth factor receptor (FGFR) 2 is an established prognostic factor and treatment target in gastric cancer. However, the roles of other FGFRs have not been fully elucidated. In this study, we investigated the correlations of the expression of FGFR1-4 with clinicopathological characteristics and outcomes in gastric cancer. Tumor samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy between 2003 and 2007. The expression of each FGFR was measured in the tumors by immunohistochemical analysis. The overexpression of FGFR1, FGFR2 or FGFR4 was found to be significantly associated with tumor progression, including depth of invasion, lymph node metastasis, pathological stage and distant metastasis or recurrent disease. Patients exhibiting overexpression of FGFR1, FGFR2 or FGFR4 had a significantly poorer disease-specific survival (DSS; P<0.001, P=0.008 and P<0.001, respectively). Moreover, the co-overexpression of all three FGFRs was significantly associated with a poorer DSS compared to the expression of none or only one of the FGFRs (P<0.001 and P=0.001, respectively) and it was found to be an independent prognostic factor (HR=1.71, 95% CI: 1.02-2.85, P=0.041). In conclusion, high expression of FGFR1, FGFR2 or FGFR4 was associated with tumor progression and poor survival in patients with gastric cancer. Similar to FGFR2, FGFR1 and FGFR4 may be considered as prognostic factors and treatment targets in gastric cancer.

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Section: Metastatic Lymph Nodescontrasting

confidence: 56%

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer

Murase

Inokuchi

Takagi

et al. 2014

Molecular and Clinical Oncology

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“…Recently, the association between FGFR3 expression and clinicopathological/molecular parameters of prognosis was evaluated by immunohistochemistry in 50 invasive breast cancer specimens [44]. In that study, the authors suggest that FGFR3 expression in invasive breast cancer might be used as a candidate marker for poor prognosis.…”

Section: Selection Of 3 H After E 2 Stimulation As An Appropriate Timmentioning

confidence: 99%

Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland

Calvo

Luu‐The

Belleau

et al. 2012

Breast Cancer Res Treat

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Novel agents for the endocrine therapy of breast cancer are needed, especially in order to take advantage of the multiple consecutive responses observed in metastatic progressing breast cancer following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its frequent poor tolerance and serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen which represents a unique opportunity to achieve the most potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues, especially the bones. To better understand the specificity of action of ACOL, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as to the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E(2)) and to induce effects of their own on the genomic profile in the mouse mammary gland. The genes modulated by E(2) were those identified in two separate experiments and validated by quantitative real-time PCR (qPCR). Three hours after the single subcutaneous injection of E(2) (0.05 μg), the simultaneous administration of ACOL, fulvestrant, tamoxifen, and raloxifene blocked by 98, 61, 43, and 92 % the number of E(2)-upregulated genes, respectively. On the other hand, 70, 10, 25, and 55 % of the genes down-regulated by E(2) were blocked by the same compounds. Of the 128 genes modulated by E(2), 49 are associated with tumorigenesis while 22 are known to be associated with breast cancer. When used alone, ACOL modulated the smallest number of genes also influenced by E(2), namely 4 %, thus possibly explaining potential utilities of this compound in breast cancer prevention and therapy.

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“…This triggers the recruitment of adaptor proteins, such as FGFR substrate 2a (FRS2a), leading to activation of several downstream signaling cascades, including the Ras-Raf-MAPK, PI3K-Akt-mTOR, and phospholipase C g (PLCg) pathways. Dysregulation and activation of FGFR3 through a variety of mechanisms has been identified in a wide spectrum of human cancers, including multiple myeloma (6)(7)(8), squamous cell carcinoma of the lung (9, 10), breast cancer (11,12), glioblastoma (13,14), testicular cancer (15), and bladder cancer (16).…”

Section: Introductionmentioning

confidence: 99%

MMP-1 and Pro-MMP-10 as Potential Urinary Pharmacodynamic Biomarkers of FGFR3-Targeted Therapy in Patients with Bladder Cancer

Du¹,

Lin²,

Wang³

et al. 2014

Clinical Cancer Research

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Purpose: The aim of this study was to identify noninvasive pharmacodynamic biomarkers of FGFR3-targeted therapies in bladder cancer to facilitate the clinical development of experimental agent targeting FGFR3.Experimental Design: Potential soluble pharmacodynamic biomarkers of FGFR3 were identified using a combination of transcriptional profiling and biochemical analyses in preclinical models. Two matrix metalloproteinases (MMP), MMP-1 and MMP-10, were selected for further studies in human bladder cancer xenograft models treated with a specific anti-FGFR3 monoclonal antibody, R3Mab. Serum and urinary levels of MMP-1 and MMP-10 were determined in healthy donors and patients with bladder cancer. The modulation of MMP-1 and MMP-10 by R3Mab in patients with bladder cancer was further evaluated in a phase I dose-escalation study.Results: MMP-1 and MMP-10 mRNA and protein were downmodulated by FGFR3 shRNA and R3Mab in bladder cancer cell lines. FGFR3 signaling promoted the expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. In bladder cancer xenograft models, R3Mab substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, both MMP-1 and pro-MMP-10 were elevated in the urine of patients with advanced bladder cancer. In a phase I dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in patients with bladder cancer.Conclusion: These findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for R3Mab in patients with bladder cancer. Clin Cancer Res; 20(24); 6324-35. Ó2014 AACR.

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Immunohistochemical Detection of Fibroblast Growth Factor Receptor 3 in Human Breast Cancer: Correlation with Clinicopathological/Molecular Parameters and Prognosis

Cited by 23 publications

References 56 publications

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer

Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland

MMP-1 and Pro-MMP-10 as Potential Urinary Pharmacodynamic Biomarkers of FGFR3-Targeted Therapy in Patients with Bladder Cancer

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