The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas

Paliga, Aleksandra; Marginean, Horia; Tessier‐Cloutier, Basile; Purgina, Bibianna; Jonker, Derek J.; Marginean, Esmeralda Celia

doi:10.1097/coc.0000000000000202

Cited by 10 publications

(7 citation statements)

References 87 publications

(120 reference statements)

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“…The addition of anti-EGFR antibodies to chemotherapy has shown a synergistic effect in preclinical models overexpressing EGFR [ 30 ]. However, EGFR overexpression has been shown in 15% of gastric carcinomas by immunohistochemistry [ 10 ], while amplification of EGFR was noted in 1-7% of cases [ 31 , 32 ]. EGFR overexpression and amplification may be predictive of a response to anti-EGFR agents, as has been reported in a small phase II study [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The first member of this family (epidermal growth factor receptor: EGFR/HER-1) has been found to be frequently altered in several carcinomas and is related to tumorigenesis [ 8 ]. In gastric adenocarcinomas, overexpression of EGFR has been observed in up to 55% of cases [ 9 ] and its overexpression has been associated with an adverse clinical prognosis [ 10 , 11 ]. Therefore, since EGFR represents a targetable pathway in advanced/metastatic gastric cancer, trials were conducted with either the anti-EGFR monoclonal antibody cetuximab [ 12 ] or the tyrosine kinase inhibitor gefitinib [ 13 ], resulting in some responses.…”

Section: Introductionmentioning

confidence: 99%

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Panitumumab in combination with modified docetaxel/ cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group

Kentepozidis

Economopoulou

Liontos

et al. 2018

aog

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BackgroundA phase I/II study to define the maximum tolerated dose (MTD) of biweekly docetaxel/cisplatin/5-fluorouracil (DCF) plus panitumumab (P), its efficacy, and tolerability as first-line treatment in advanced gastroesophageal cancer.MethodsIn phase I part, patients with unresectable locally advanced or metastatic adenocarcinomas of the stomach or the gastroesophageal junction received cisplatin (40 mg/m2 on day 1), leucovorin (400 mg/m2 on day 1), 5-fluorouracil (400 mg/m2 bolus on day 1), 5-fluorouracil (1000 mg/m2/daycontinuous infusion on days 1-2), and escalated doses of docetaxel (on day 1) plus P (6 mg/kg on day 1) every 2 weeks. In phase II part, patients were treated with DCF/P at the MTD and the primary endpoint was response rate. The expected response rate was set at >40%.ResultsThe MTD for docetaxel in the mDCF/P was defined at 40 mg/m2 and a total of 40 evaluable patients were enrolled in phase II study. One (2.5%) complete and 13 (32.5%) partial responses (overall response rate: 35%), as well as 16 (40%) disease stabilizations were documented. The median progression-free survival was 6.9 months (95% confidence interval [CI] 3.5-10.3) and the median overall survival was 11.3 months (95%CI 7.7-14.8). Grade 3-4 neutropenia occurred in 10 patients (25%) and febrile neutropenia in 2 (5%). Allergic reactions (grade 1-4) occurred in 9 patients (22.5%). There was 1 treatment-related death.ConclusionsmDCF/P combination was feasible, though associated with a poor toxicity profile. However, the study failed to meet its primary endpoint and was terminated prematurely due to futility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Panitumumab in combination with modified docetaxel/ cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group

Kentepozidis

Economopoulou

Liontos

et al. 2018

aog

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“…The data from all eligible studies 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 were extracted by two independent authors and the extracted data were the first author's name, year of publication, study location, antibody clone and manufacturer, antibody dilution ratio, evaluation criteria, number of patients analyzed, and the data allowing the estimation of the impact of c-MET overexpression as determined by IHC on overall survival (OS). For the meta-analysis, we extract ed all the data associated with the results of the IHC analyses.…”

Section: Methodsmentioning

confidence: 99%

Clinicopathological Significance and Diagnostic Accuracy of c-MET Expression by Immunohistochemistry in Gastric Cancer: A Meta-Analysis

2016

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PurposeThe aim of the present study was to elucidate the clinicopathological significance and diagnostic accuracy of immunohistochemistry (IHC) for determining the mesenchymal epidermal transition (c-MET) expression in patients with gastric cancer (GC).Materials and MethodsThe present meta-analysis investigated the correlation between c-MET expression as determined by IHC and the clinicopathological parameters in 8,395 GC patients from 37 studies that satisfied the eligibility criteria. In addition, a concordance analysis was performed between c-MET expression as determined by IHC and c-MET amplification, and the diagnostic test accuracy was reviewed.ResultsThe estimated rate of c-MET overexpression was 0.403 (95% confidence interval [CI], 0.327~0.484) and it was significantly correlated with male patients, poor differentiation, lymph node metastasis, higher TNM stage, and human epidermal growth factor receptor 2 (HER2) positivity in IHC analysis. There was a significant correlation between c-MET expression and worse overall survival rate (hazard ratio, 1.588; 95% CI, 1.266~1.992). The concordance rates between c-MET expression and c-MET amplification were 0.967 (95% CI, 0.916~0.987) and 0.270 (95% CI, 0.173~0.395) for cases with non-overexpressed and overexpressed c-MET, respectively. In the diagnostic test accuracy review, the pooled sensitivity and specificity were 0.56 (95% CI, 0.50~0.63) and 0.79 (95% CI, 0.77~0.81), respectively.ConclusionsThe c-MET overexpression as determined by IHC was significantly correlated with aggressive tumor behavior and positive IHC status for HER2 in patients with GC. In addition, the c-MET expression status could be useful in the screening of c-MET amplification in patients with GC.

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“…The study of c-Met expression in GC is helpful for the analysis of GC subtypes and conducive to the selection and optimization of targeted therapy methods for GC. Its expression in GC and its relationship with the prognosis of patients have always been a research hotspot [17][18][19]. However, data on c-Met in GC are still scarce, so understanding their characteristics is essential to improve treatment outcomes and survival in these patients.…”

Section: Introductionmentioning

confidence: 99%

Study on the expression of c-Met in gastric cancer and its correlation with blood tumor markers and prognosis

Zhang

Miao

Wang

et al. 2022

Preprint

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Background: Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with blood tumor markers and prognosis. In order to provide a new idea and method for targeting c-Met in the treatment of GC.Methods: Ninety-seven patients who underwent GC surgery in our hospital from December 2013 to September 2015 were included in this study. The tissue microchip was constructed by paraffin cutting, including 97 GC points and 83 para-cancer points. Then, it was used for c-Met immunohistochemical staining, followed by immunological H-score. The expression of c-Met was compared with clinicopathological features, blood tumor markers (AFP, CEA, CA199, CA153, CA125, CA50) and 5-year survival. Descriptive statistics, Pearson correlation test, Kaplan-Meyer survival curve and COX regression were used for statistical analysis.Results: The high expression rate of c-Met was 64.95% (63/97) in GC tissues, and 28.92% (24/83) in para-cancer tissues. There were prominent statistical differences in the M-stage and clinicopathological stage between the low and high expression groups (P<0.05), the c-Met high expression group also had a higher M-stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (P=0.004), indicating a positive correlation. High c-Met expression correlated with poor overall survival (OS) for 5 years (HR=2.103, P=0.005). After the clinicopathological classification of patients, it was found that the high expression of c-Met in stage Ⅰ-Ⅱ patients was correlative with poor OS for 5 years (HR=2.486, P=0.026), while stage Ⅲ-Ⅳ patients had no statistical significance (P>0.05). Univariate and multivariate COX regression analysis showed that age, clinicopathological stage, c-Met high expression and preoperative serum AFP might be independent risk factors for survival 5 years after surgery.Conclusion: This study found that the high expression of c-Met in GC was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after GC surgery. The expression of c-Met in GC was positively correlated with preoperative serum CA125.

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The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas

Cited by 10 publications

References 87 publications

Panitumumab in combination with modified docetaxel/ cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group

Panitumumab in combination with modified docetaxel/ cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group

Clinicopathological Significance and Diagnostic Accuracy of c-MET Expression by Immunohistochemistry in Gastric Cancer: A Meta-Analysis

Study on the expression of c-Met in gastric cancer and its correlation with blood tumor markers and prognosis

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