Homogeneous EGFR amplification defines a subset of aggressive Barrett’s adenocarcinomas with poor prognosis

Marx, Andreas; Zielinski, M.; Kowitz, Charlotte Marie; Dancau, Ana Maria; Thieltges, Sabrina; Simon, Ronald; Choschzick, Matthias; Yekebas, Emre F.; Kaifi, Jussuf T.; Mirlacher, Martina; Atanackovic, Djordje; Brümmendorf, Tim H.; Fiedler, Walter; Bokemeyer, Carsten; Izbicki, Jakob R.; Sauter, Guido

doi:10.1111/j.1365-2559.2010.03643.x

Cited by 33 publications

(30 citation statements)

References 48 publications

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“…It was really a huge consumption because the TMA was difficult to collect and construct. In our future research, we will try to improve the IHC protocols, such as applying the isotope antibody for the negative control which has been demonstrated as a reliable option in IHC analysis (Marx et al, 2010;Xiang et al, 2014), to make the experiments more operative and effective. For another, although KPS has been widely used as a functional assessment tool for performance status in oncology and it has been proved useful as outcome predictor for cancer patients (Abernethy et al, 2005;Péus et al, 2013), it failed to exhibit the prognostic significance in IDC in this present study.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

Xu¹,

Tang²,

Lu³

et al. 2014

Experimental and Molecular Pathology

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Section: Discussionmentioning

confidence: 99%

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

Xu¹,

Tang²,

Lu³

et al. 2014

Experimental and Molecular Pathology

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“…(B) High level EGFR amplification. EGFR amplification was detected as clusters of numerous red fluorescent signals which is a characteristic pattern caused by high EGFR copy number (see reference [57]) with variable chromosome 7 centromere copy number. (C) Tumor cells with a near normal MYC and centromere 8 copy number.…”

Section: Resultsmentioning

confidence: 99%

The Degree of Segmental Aneuploidy Measured by Total Copy Number Abnormalities Predicts Survival and Recurrence in Superficial Gastroesophageal Adenocarcinoma

et al. 2014

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BackgroundPrognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC.MethodsWe quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses.ResultsRecurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables.SignificanceSNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC.

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“…According to the study by Owonikoko et al (20), more EGFR gene amplification was detected in the tumor tissue center than in the periphery. In another study (15), identical EGFR amplification status was found in Barrett's adenocarcinoma primary tumors and corresponding lymph node metastases.…”

Section: Egfr and Barrett's Esophagusmentioning

confidence: 95%

“…Autonomous activation of EGFR amplifies tumorigenic processes, from metaplasia, low-grade dysplasia, high-grade dysplasia to adenocarcinoma (14). NF-κB-CDX2 axis activation (15) and COX-2 upregulation (8) have been observed in this process. EGFR-positive expression was observed in 60% of Barrett's-associated adenocarcinoma (16).…”

Section: Egfr and Barrett's Esophagusmentioning

confidence: 99%

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of esophageal carcinoma and the suggested mechanisms of action

Sheng

Mao

2012

Oncology Letters

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Abstract. Cumulative evidence indicates that epidermal growth factor receptor (EGFR) is one of the most commonly altered genes in human cancer, via overexpression, amplification and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation and resistance to apoptosis. Small molecule tyrosine kinase inhibitors (TKIs) are among the most common EGFR-targeting agents and have been used clinically to treat various malignancies. This review discusses the mechanism of action and clinical data that are relevant to the use of EGFR-TKIs in the treatment of esophageal carcinoma. The clinical and basic scientific experience of these agents thus far have implications for the future of therapeutic targeting of EGFR.

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Homogeneous EGFR amplification defines a subset of aggressive Barrett’s adenocarcinomas with poor prognosis

Abstract: The high level and homogeneity of EGFR amplification in primary tumours and metastases suggests the potential therapeutic utility of anti-EGFR drugs in BAC.

Cited by 33 publications

References 48 publications

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

The Degree of Segmental Aneuploidy Measured by Total Copy Number Abnormalities Predicts Survival and Recurrence in Superficial Gastroesophageal Adenocarcinoma

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of esophageal carcinoma and the suggested mechanisms of action

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