Recurrent gene amplifications in human type I endometrial adenocarcinoma detected by fluorescence in situ hybridization

Samuelson, Emma; Levan, Kristina; Adamović, Tatjana; Levan, Göran; Horváth, György

doi:10.1016/j.cancergencyto.2007.11.006

Cited by 17 publications

(12 citation statements)

References 15 publications

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“…It should be stressed that the rat disease genes identified so far have shown remarkable relevance to related human disease phenotypes (Aitman et al 2008, Samuelson et al 2008. Furthermore, there are instances that the rat model has inspired new therapeutic approaches (Gelderman et al 2007, Pravenec & Kurtz 2007.…”

Section: E Samuelson Et Al: Molecular Classification Of Bdii Rat Eacmentioning

confidence: 99%

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Samuelson

Hedberg²,

Nilsson³

et al. 2009

Endocrine-Related Cancer

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Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (b-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.

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Section: E Samuelson Et Al: Molecular Classification Of Bdii Rat Eacmentioning

confidence: 99%

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Samuelson

Hedberg²,

Nilsson³

et al. 2009

Endocrine-Related Cancer

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“…MET gene mutation has been found mainly in hereditary papillary renal cell carcinoma (Schmidt et al , 1997) and in a subset of lung cancer (Ma et al , 2003). Previous studies described MET gene amplification (GA) in 4% of non-small-cell lung cancers (Cappuzzo et al , 2009; Go et al , 2010), in 4% of oesophageal cancer (Miller et al , 2005), and in endometrial cancer (Samuelson et al , 2008). In gastric cancer, it has been reported that MET amplification was found in 0–23% of gastric cancers, and MET overexpression and/or GA was associated with advanced disease stage and/or worse clinical outcome (Hara et al , 1998; Nakajima et al , 1999; Huang et al , 2001; Amemiya et al , 2002; Graziano et al , 2011; Janjigian et al , 2011; Lee et al , 2011; Lennerz et al , 2011; Zhao et al , 2011; Toiyama et al , 2012).…”

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confidence: 99%

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome

et al. 2012

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Background:The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.Methods:MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.Results:Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.Conclusion:MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

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“…(14–18, 27–33) Hepatocyte growth factor (HGF), which is a plasminogen-like protein that was considered a humoral mediator of liver regeneration, has been shown to be the c-Met proto-oncogene product. (13, 34) Pennacchietti S. et al (35) studied various in vitro cell lines including cervical cancer to find that hypoxia promotes tumor invasion by sensitizing cells to HGF stimulation, which explains the molecular basis of c-Met overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…(13–20) Baykal et al (14) reported c-Met overexpression in 60% of early stage cervical cancer patients (FIGO stage IB disease, treated primarily with surgery). Other studies reported c-Met gene overexpression in up to 11% of patients with lung cancer, (15) 10% of gastric cancers, (16) and 4% of endometrial and esophageal cancers (17, 18) .…”

Section: Introductionmentioning

confidence: 96%

c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target

Refaat

Donnelly

Sachdev

et al. 2017

American Journal of Clinical Oncology

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Purpose This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation (CRT) and treatment outcomes including overall survival (OS), progression free survival (PFS), distant metastases control (DM), and local-regional control (LC). Patients and Methods This IRB approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semi-quantitatively by three pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score). Treatment- outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses. Results The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%), and 18 patients (64.3%) had c-Met H-index > 30 and < 30, respectively. c-Met overexpression was significantly associated with worse 3-year and 5-year OS (p= 0.003), PFS (p = 0.002), LC (p = 0.01), and DC (p = 0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and distant metastases, respectively. Conclusion c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.

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Recurrent gene amplifications in human type I endometrial adenocarcinoma detected by fluorescence in situ hybridization

Cited by 17 publications

References 15 publications

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome

c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target

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