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Brunner, M; Thurnher, D; Pammer, J; Geleff, S; Heiduschka, G; Reinisch, CM; Petzelbauer, P; Erovic, BM.
Expression of VEGF-A/C, VEGF-R2, PDGF-alpha/beta, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma.
Mod Pathol. 2008; 21(7):876-884 Doi: 10.1038/modpathol.2008.63 [OPEN ACCESS]
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Leading authors Med Uni Graz: Brunner Markus
Co-authors Med Uni Graz: Thurnher Dietmar
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Abstract:: Merkel cell carcinoma is a rare but very aggressive tumor of the skin. With current treatment options, Merkel cell carcinoma is associated with a high incidence of recurrence and metastasis. Targeted anticancer therapies such as receptor tyrosine kinase inhibitors and antisense oligonucleotides have been found to be a promising new type of treatment for various types of cancer. To evaluate whether the use of targeted therapies is a possible treatment option in Merkel cell carcinoma, we determined the expression of the target molecules c-kit, Mcl-1, Bmi-1, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-receptor 2 (VEGF-R2), platelet-derived growth factor (PDGF)-alpha, PDGF-beta, epidermal growth factor receptor (EGFR) and Her-2/Neu in a tissue microarray of 32 samples of 29 patients with Merkel cell carcinoma. C-kit-positive samples were analyzed for mutations in exons 9 and 11. The tissue microarray was stained immunohistochemically with antibodies directed against the above-mentioned proteins, and an immunoreactivity score was calculated. DNA was extracted from c-kit-positive samples and was analyzed for exon 9 and 11 mutations using direct DNA sequencing. We found that c-kit (7%), Mcl-1 (88%), Bmi-1 (78%), VEGF-A (91%), VEGF-C (75%) VEGF-R2 (88%), PDGF-alpha (72%) and PDGF-beta (13%) were expressed in Merkel cell carcinomas. All samples showed a lack of EGFR and Her-2/Neu expression. Analysis of c-kit revealed no mutations. As VEGF-A, VEGF-C, VEGF-R2, PDGFs and c-kit are targets of new cytostatic agents used in the treatment of other cancers, inhibition by a multitargeted chemotherapy could be a very promising treatment option. High expression of Bmi-1 and Mcl-1 warrants further studies on the use of antisense oligonucleotides in Merkel cell carcinoma.
Find related publications in this database (using NLM MeSH Indexing): Aged -; Austria - epidemiology; Biomarkers, Tumor - metabolism; Carcinoma, Merkel Cell - metabolism; Carcinoma, Merkel Cell - mortality; Carcinoma, Merkel Cell - secondary; DNA Mutational Analysis -; Disease-Free Survival -; Female -; Fluorescent Antibody Technique, Indirect -; Humans -; Immunoenzyme Techniques -; Male -; Myeloid Cell Leukemia Sequence 1 Protein -; Neoplasm Proteins - metabolism; Nuclear Proteins - metabolism; Platelet-Derived Growth Factor - metabolism; Polycomb Repressive Complex 1 -; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - metabolism; Repressor Proteins - metabolism; Skin Neoplasms - metabolism; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Survival Rate -; Vascular Endothelial Growth Factor A - metabolism
Find related publications in this database (Keywords): merkel cell carcinoma; targeted therapies; receptor tyrosine kinase; c-kit; Bmi-1; Mcl-1