Isis Atallah

Publications (3)15.17 Total impact

• Article: MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors.

  Nikola Holtkamp, Isis Atallah, Ali-Fuat Okuducu, Jana Mucha, Christian Hartmann, Victor-F Mautner, Reinhard E Friedrich, Christian Mawrin, Andreas von Deimling
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  ABSTRACT: Malignant peripheral nerve sheath tumors (MPNST) are sarcomas with poor prognosis and limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 non-NF1 patients, and 14 neurofibroma patients for matrix metalloproteinase 13 (MMP-13) expression. Because wild-type and mutant p53 were shown to differentially regulate MMP-13 expression, TP53 status and protein levels were also determined. MMP-13 expression was detected in 58% of MPNST and was significantly associated with recurrent MPNST (P = .019). p53 was observed in 78% of MPNST and was found to be strongly associated with MMP-13 expression (P = .005). In contrast, 14 neurofibromas lacked MMP-13 and p53 expressions. TP53 mutations were found in only 11% of MPNST and were associated with high tumor grades (P = .029). No significant association between mutant TP53 and MMP-13 was observed, indicating that other factors drive MMP-13 expression in MPNST. The presence of metastasis was linked to p53Pro(72) polymorphism (P = .041) and shorter survival. In summary, our data suggest that MMP-13 expression in nerve sheath tumors is coupled with malignant progression. Therefore, MMP-13 may serve as a marker for progression and as a therapeutic target.
  Neoplasia (New York, N.Y.) 09/2007; 9(8):671-7. · 5.48 Impact Factor
• Article: Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity.

  Nikola Holtkamp, Ali Fuat Okuducu, Jana Mucha, Anastasia Afanasieva, Christian Hartmann, Isis Atallah, Lope Estevez-Schwarz, Christian Mawrin, Reinhard E Friedrich, Victor-F Mautner, Andreas von Deimling
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  ABSTRACT: Platelet-derived growth factor receptor alpha (PDGFRalpha) and c-Kit are receptor tyrosine kinases. Both are targets of the tyrosine kinase inhibitor imatinib mesylate which is approved for treatment of some cancers. In order to assess the role of PDGFRalpha and c-Kit in malignant peripheral nerve sheath tumours (MPNST) we examined human tumours for structural alterations, protein and ligand expression. We investigated 34 MPNST, 6 corresponding plexiform neurofibromas (pNF) and 1 MPNST cell culture from 31 patients for mutations and polymorphisms in PDGFRA (exon 2-21) and KIT (exon 9, 11, 13, 17). PDGFRA was amplified in seven tumours from six patients and MPNST cell culture S462. KIT was amplified in five tumours from four patients and in the cell culture. Two MPNST carried somatic PDGFRA mutations in exons coding for the extracellular domain. In addition we detected several polymorphisms in PDGFRA. No point mutations or polymorphisms were detected in the four KIT exons analysed. PDGFRalpha expression was present in 21 of 28 MPNST patients (75%) and the MPNST cell culture. Expression analysis of PDGFRalpha ligands in MPNST and neurofibromas revealed that PDGF-A was more widely expressed than PDGF-B. Focal c-Kit expression was detected in 2 of 29 (7%) MPNST patients. Imatinib treatment of MPNST cell culture S462 exerted a growth inhibitory effect and prevented PDGF-AA induced PDGFRalpha phosphorylation. In summary, PDGFRA, PDGF and KIT dysregulation as well as growth inhibition of cell culture S462 by imatinib may suggest that MPNST patients benefit from treatment with imatinib.
  Carcinogenesis 04/2006; 27(3):664-71. · 5.70 Impact Factor
• Article: Subclassification of nerve sheath tumors by gene expression profiling.

  Nikola Holtkamp, David E Reuss, Isis Atallah, Ralf-Jürgen Kuban, Christian Hartmann, Victor-F Mautner, Silke Frahm, Reinhard E Friedrich, Bernd Algermissen, Van-Anh Pham, Sandra Prietz, Thorsten Rosenbaum, Lope Estevez-Schwarz, Andreas von Deimling
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  ABSTRACT: Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas plexiform neurofibromas are only observed in one-third of the patients. NF1-patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1-patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1-associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.
  Brain Pathology 08/2004; 14(3):258-64. · 3.99 Impact Factor