Marlies Schrevel

Publications (3)20.14 Total impact

• Article: Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer.

  Marlies Schrevel, Arko Gorter, Sandra M Kolkman-Uljee, J Baptist M Z Trimbos, Gert Jan Fleuren, Ekaterina S Jordanova
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  ABSTRACT: The epidermal growth factor receptor is overexpressed in 70-90% of cervical cancers. Previously, we have shown that epidermal growth factor receptor overexpression independently predicts poor prognosis in cervical cancer patients, which makes it a potential therapeutic target. The aim of this study was to systematically analyze the molecular mechanism leading to epidermal growth factor receptor overexpression in cervical cancer. All experiments were performed on archival paraffin-embedded material. In 166 cervical cancer patients, cytoplasmic, membrane and phosphorylated epidermal growth factor receptor protein expression were studied in association with patient survival. Membrane epidermal growth factor receptor overexpression was associated with poor disease-specific survival (P=0.027). This association was particularly present in human papillomavirus 16-positive patients (P=0.029). We analyzed whether epidermal growth factor receptor overexpression was caused by gene amplification using fluorescence in situ hybridization. Epidermal growth factor receptor gene copy number was linked to chromosome 7 ploidy, as no gene amplification could be detected when corrected for chromosome 7 centromeric signals. Chromosome 7 aneuploidy was associated with membrane epidermal growth factor receptor overexpression (P=0.013). Additional mutation analysis was performed by sequencing pure, flow-sorted tumor cells, but no mutations were detected. Furthermore, human papillomavirus 16 E5 and E6 oncogene mRNA expression was measured, using quantitative real-time polymerase chain reaction, to determine the association between the human papillomavirus and epidermal growth factor receptor overexpression. High human papillomavirus 16 E5 and E6 mRNA expression were associated with decreased survival (P=0.045 and 0.047, respectively). High human papillomavirus 16 E6 mRNA expression was associated with membrane epidermal growth factor receptor overexpression (P=0.013). This is the first study performed on cancer patient material showing that chromosome 7 aneuploidy and high human papillomavirus 16 E6 mRNA expression lead to membrane epidermal growth factor receptor overexpression in cervical cancer.
  Modern Pathology 01/2011; 24(5):720-8. · 4.79 Impact Factor
• Article: Platelet receptor P2RY12 haplotypes predict restenosis after percutaneous coronary interventions.

  Goran Rudez, Douwe Pons, Frank Leebeek, Pascalle Monraats, Marlies Schrevel, Aeilko Zwinderman, Robbert de Winter, René Tio, Pieter Doevendans, Wouter Jukema, Moniek de Maat
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  ABSTRACT: The platelet receptor P2Y12 (gene symbol P2RY12) is involved in several processes that contribute to restenosis after percutaneous coronary interventions (PCI). Therefore, common variation in the P2Y12 gene may serve as a useful marker for risk stratification. We studied whether common variation in the platelet receptor P2Y12 gene affects the risk of restenosis after PCI. Comprehensive coverage of common variation in the P2Y12 gene was obtained by genotyping five haplotype-tagging SNPs (ht-SNPs) in 2,062 PCI-treated patients who received a stent and participated in the GENetic DEterminants of Restenosis (GENDER) Study. Haplotypes were inferred and their association with target vessel revascularization (TVR) was studied. Seven P2Y12 haplotypes were identified with an allelic frequency above 5% (designated here H1 to H7) of which two (H5 and H7) were associated with a higher risk of TVR (hazard ratios [HR]=1.4, 95% confidence interval [CI]=1.0-2.0; and HR=1.6, 95% CI=1.2-2.0, respectively) than the reference P2Y12 haplotype (H1), which contains the common alleles of all five P2Y12 ht-SNPs. Our study shows that common variation in the P2Y12 gene predicts restenosis in PCI-treated patients.
  Human Mutation 04/2008; 29(3):375-80. · 5.69 Impact Factor
• Article: Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation.

  Mandy G Keijzer-Veen, Marlies Schrevel, Martijn J J Finken, Friedo W Dekker, Jeroen Nauta, Elysée T M Hille, Marijke Frölich, Bert J van der Heijden
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  ABSTRACT: This prospective follow-up study of 422 19-yr-old subjects born very preterm in The Netherlands was performed to determine whether intrauterine growth retardation (IUGR) predisposes to abnormal GFR and microalbuminuria in adolescents. GFR (ml/min per 1.73 m2) was estimated using the Cockcroft-Gault equation, and albumin-creatinine ratio (mg/mmol) was calculated in a cohort of 19-yr-old subjects born very preterm (gestational age <32 wk) in 1983. Birth weights were adjusted for gestational age and expressed as standard deviation scores (sds) as a measure of IUGR. All subjects had normal renal function. Birth weight (sds) was associated negatively with serum creatinine concentration (micromol/L) (beta = -1.0 micromol/L, 95% confidence interval [CI]: -1.9 to -0.2), positively with GFR (beta = 3.0, 95% CI: 1.7 to 4.2), and negatively with the logarithm of albumin-creatinine ratio (beta = -0.05, 95% CI: -0.09 to -0.01) in young adults born very preterm. IUGR is associated with unfavorable renal functions at young adult age in subjects born very premature. These data suggest that intrauterine growth-retarded subjects born very premature have an increased risk to develop progressive renal failure in later life.
  Journal of the American Society of Nephrology 09/2005; 16(9):2762-8. · 9.66 Impact Factor