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77th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

24.05. - 28.05.2006, Mannheim

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Investigations of the B-RAF-MAPK and PTEN/PI3K-Signaling Pathways in Melanoma

Untersuchungen der B-RAF-MAPK und PTEN/PI3K-Signaltransduktionswege in Melanomen

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German Society of Otorhinolaryngology, Head and Neck Surgery. 77th Annual Meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery. Mannheim, 24.-28.05.2006. Düsseldorf, Köln: German Medical Science; 2006. Doc06hno060

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hno2006/06hno060.shtml

Published: September 7, 2006

© 2006 Affolter et al.
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The RAS-RAF-MEK-ERK cascade is an intracellular signaling pathway that controls cell fate. The pathway plays an important role in different types of cancer. In 50-70% of melanomas, MEK–ERK signaling is elevated due to B-RAF mutations. Altered V600E-B-RAF has 500-fold elevated kinase activity leading to constitutive MEK-ERK stimulation and therefore to proliferation and survival in cancer cells. Thus, B-RAF is an important and exciting therapeutic target.

The PTEN/PI3K-Akt cascade is another example for a signaling pathway that is often deregulated in melanoma.

We have investigated tumour and skin samples of melanoma patients on different clinical trials. The samples were analysed for alterations in the RAS/RAF/MEK/ERK and PTEN/PI3K-Akt pathways by direct sequencing and immunohistochemistry.

None of the samples showed mutations in N-Ras and K-Ras or PI3K. 5 out of 9 tumours analysed harboured mutations in B-RAF Exon 15. 9/9 and 6/9 melanoma samples expressed phosphorylated (pp-) MEK and phosphorylated (pp-) ERK in the cytoplasm. No correlation could be detected between mutational status and protein expression, however. Therefore pp-MEK and pp-ERK could not be used as surrogate markers to identify which cancers carried B-RAF mutations in this analysis. Furthermore our study did not give evidence that PI3K mutations might play a role in the development of melanomas.