FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors

Carracedo, Alma; Égervári, Kristóf; Salido, Marta; Rojo, Federico; Corominas, Josep; Arumí, Montserrat; Corzo, Cristina; Tusquets, Ignacio; Espinet, Blanca; Rovira, Ana; Albanell, Joan; Szöllősi, Zoltán; Serrano, Sergi; Solé, Françesc

doi:10.1186/bcr2239

Cited by 24 publications

(24 citation statements)

References 4 publications

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“…It is unclear what is causing this overexpression, a common cause is known to be gene amplification. Previous studies have failed to find MET amplification in breast cancer [20, 21]; the present study showed MET amplification in only 8% of the tumours of two cohorts, and amplification did not correlate with protein expression. Although protein expression did not correlate with poor prognosis, increased MET copy number tended in both cohorts to be indicative of a shortened distant and loco-regional recurrence-free survival.…”

Section: Discussioncontrasting

confidence: 87%

Met and its ligand HGF are associated with clinical outcome in breast cancer

et al. 2016

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Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo- or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre- and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the pre-menopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested.

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Section: Discussioncontrasting

confidence: 87%

Met and its ligand HGF are associated with clinical outcome in breast cancer

et al. 2016

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“…24 The expression rate of MET protein has been reported to vary from 15.0 to 72.7%. 34 This wide range in MET expression could primarily be the consequence of using different antibodies for immunohistochemical analysis and different threshold criteria for positivity (Supporting Information 5). SP44 monoclonal antibody (Ventana) showed clear membranous staining in positive cases without background staining.…”

Section: Discussionmentioning

confidence: 99%

MET is a potential target for use in combination therapy with EGFR inhibition in triple-negative/basal-like breast cancer

et al. 2013

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MET, a cell surface receptor for hepatocyte growth factor, is involved in the development of triple-negative/basal-like breast cancer (TNBC/BLBC). However, its utility as a therapeutic target in this subtype of breast cancer is poorly understood. To evaluate MET fully as a potential therapeutic target for TNBC/BLBC, we investigated the relationship between MET expression and clinical outcomes of patients with breast cancer and the functional effect of MET inhibition. Using automated immunohistochemistry (Ventana), we analyzed MET expression in 924 breast cancer patients with relevant clinicopathologic parameters. BLBC showed the strongest relationship with MET expression (57.5%, p < 0.001). High expression of MET in breast cancer resulted in poor overall survival (p 5 0.001) and disease-free survival (DFS, p 5 0.010). MET expression was relatively high in TNBC cell lines, and the silencing of MET via small interfering RNA reduced cell proliferation and migration. We observed reduced TNBC cell viability after treatment with the MET inhibitor PHA-665752. In the most drug-resistant cell line, MDA-MB-468, which showed elevated epidermal growth factor receptor (EGFR) expression, silencing of EGFR resulted in increased sensitivity to PHA-665752 treatment. We confirmed that PHA-665752 synergizes with the EGFR inhibitor erlotinib to decrease the viability of MDA-MB-468 cells. TNBC patients coexpressing MET and EGFR showed significantly worse DFS than that in patients expressing EGFR alone (p 5 0.021). Our findings strongly suggest that MET may be a therapeutic target in TNBC and that the combined therapy targeting MET and EGFR may be beneficial for the treatment of TNBC/BLBC patients.

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“…However, to date, only a few small studies have compared IHC with FISH (Carracedo et al , 2009; Janjigian et al , 2011). In this study, we evaluated MET IHC and SISH concurrently in a large archival gastric cancer cohort.…”

Section: Discussionmentioning

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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FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors

Abstract: See related research by Götte et al., http://breast-cancer-research.com/content/9/1/R8 DIC = ductal infiltrating carcinoma; ER = estrogen receptor; FISH = fluorescent in situ hybridization; PR = progesterone receptor.

Cited by 24 publications

References 4 publications

Met and its ligand HGF are associated with clinical outcome in breast cancer

Met and its ligand HGF are associated with clinical outcome in breast cancer

MET is a potential target for use in combination therapy with EGFR inhibition in triple-negative/basal-like breast cancer

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

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