Reduced membranous MET expression is linked to bladder cancer progression

Kluth, Martina; Reynolds, Kristina; Rink, Michael; Chun, Felix K.-H.; Dahlem, Roland; Fisch, Margit; Höppner, Wolfgang; Wagner, Walter; Doh, Ousman; Terracciano, Luigi; Simon, Ronald; Sauter, Guido; Minner, Sarah

doi:10.1016/j.cancergen.2014.03.008

Cited by 5 publications

(6 citation statements)

References 37 publications

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“…In a preclinical model with immortalized bronchial cells, sustained stimulation with HGF caused a gradual displacement of c-MET receptor from the membrane to the cytoplasm [ 50 ]. Also, recent studies have associated the presence of cytoplasmic Met determined by IHC with tumor progression in patients with resected bladder cancer [ 51 ] and with poor outcome in patients with gastric adenocarcinoma [ 27 ] and mesothelioma [ 50 ]. Also, the presence of a mesenchymal phenotype, which can be an early event in NSCLC [ 52 ], has been linked to poor prognosis and metastasis development in surgically resected NSCLC [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC)

et al. 2015

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ObjectiveWe aimed to assess MET intratumoral heterogeneity and its potential impact on biomarker-based patient selection as well as potential surrogate biomarkers of MET activation.MethodsOur study included 120 patients with non-squamous Non-small-cell Lung Cancer (nsNSCLC), of which 47 were incorporated in tissue microarrays (TMA). Four morphologically distinct tumor areas were selected to assess MET heterogeneity. MET positivity by immunohistochemistry (IHC) was defined as an above-median H-score and by +2/+3 staining intensity in >50% of tumor cells (Metmab criteria). MET FISH positivity was defined by MET/CEP7 ratio ≥ 2.0 and/or MET ≥ 5.0. MET staining pattern (cytoplasmic vs. membranous) and mesenchymal markers were investigated as surrogates of MET activation.ResultsMedian MET H-score was 140 (range 0–400) and 47.8% of patients were MET positive by Metmab criteria. Eight cases (6.8%) were MET FISH positive and showed higher H-scores (p = 0.021). MET positivity by IHC changed in up to 40% of cases among different tumor areas, and MET amplification in 25–50%. Cytoplasmic MET staining and positivity for vimentin predicted poor survival (p = 0.042 and 0.047, respectively).ConclusionsMET status is highly heterogeneous among different nsNSCLC tumor areas, hindering adequate patient selection for MET-targeted therapies. MET cytoplasmic staining and vimentin might represent surrogate markers for MET activation.

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Section: Discussionmentioning

confidence: 99%

MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC)

et al. 2015

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“…Figure 1 shows the flow diagram of the literature search process. Eight studies10–12,19–23 were eventually included in this meta-analysis evaluating the association between c-Met status and the clinicopathological features of bladder cancer. These studies were performed retrospectively in the following regions: China (n=5), Japan (n=1), South Korea (n=1) and Germany (n=1).…”

Section: Resultsmentioning

confidence: 99%

“…The role of c-Met in bladder cancer has also been investigated in many studies, and the results have been conflicting. Certain studies reported either a favorable association10 or an unfavorable association,11 while others showed no association12 between c-Met overexpression and the clinicopathological features of bladder cancer. Therefore, we performed this systematic review and meta-analysis to comprehensively assess the pathologic and prognostic roles of c-Met status in bladder cancer patients.…”

Section: Introductionmentioning

confidence: 99%

<p>Clinicopathological impacts of c-Met overexpression in bladder cancer: evidence from 1,336 cases</p>

Xu¹,

Zhang²,

He³

et al. 2019

OTT

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Background: The clinicopathological impacts of c-Met overexpression in bladder cancer have been investigated in several studies with conflicting results. We performed this systematic review and meta-analysis to assess the pathologic and prognostic roles of c-Met status in bladder cancer patients. Methods: Eligible studies were searched and identified from the PubMed and China National Knowledge Infrastructure (CNKI) databases (up until October 4, 2018). The DerSimonian-Laird random-effects model was used to calculate the pooled risk estimates. Results: Eight studies including 1,336 bladder cancer cases were eventually included in this meta-analysis. We detected a significantly increased risk of poor overall survival (OS) associated with the high expression of c-Met (HR=2.42, 95% CI 1.36–4.32). There was no association between c-Met status and nuclear grade (OR=0.82, 95% CI 0.29–2.31) or tumor stage (OR=1.42, 95% CI 0.41–4.89). Conclusion: This study shows that the overexpression of c-Met in primary cancer tissues is associated with a worse OS in human bladder cancer. However, larger studies using standardized methods and criteria are warranted to verify these findings.

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“…Analysis of urinary Met levels allows for differentiation of MIBC from NMIBC patients and control group. Reduced membranous Met staining is associated with unfavorable tumor phenotype …”

Section: Receptor Tyrosine Kinase Signaling: Erbb1‐3 Fgfr3 and C‐metmentioning

confidence: 99%

“…Reduced membranous Met staining is associated with unfavorable tumor phenotype. 29 Cytoskeleton Keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Its expression has been associated with worse BC prognosis.…”

Section: Cancer Stem Cell Markersmentioning

confidence: 99%

Key signaling pathways in the muscle‐invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment

Kiselyov

Bunimovich‐Mendrazitsky

Startsev

2015

Intl Journal of Cancer

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In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARc, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/ 6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance.Vast majority (>90%) of bladder carcinomas that arise from the transitional cells of the bladder mucosal epithelium are noninvasive papillary tumors that are relatively easy to deal with. However, if not detected and treated properly, at least one-third of these cancers ultimately invade the bladder wall and metastize into neighboring organs or lymph nodes by undergoing radical molecular and cellular changes. The resulting muscle-invasive bladder cancer (MIBC) is a heterogeneous group of aggressive epithelial tumors with a high rate of metastasis and poor 5-year survival rate of 30-50%. As noticed by numerous clinical research teams, the number of somatic mutations exhibited by MIBC is notoriously high.

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Reduced membranous MET expression is linked to bladder cancer progression

Cited by 5 publications

References 37 publications

MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC)

MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC)

<p>Clinicopathological impacts of c-Met overexpression in bladder cancer: evidence from 1,336 cases</p>

Key signaling pathways in the muscle‐invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment

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