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Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis

Item Type:Article
Title:Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis
Creators Name:Fecker, L.F., Geilen, C.C., Tchernev, G., Trefzer, U., Assaf, C., Kurbanov, B.M., Schwarz, C., Daniel, P.T. and Eberle, J.
Abstract:Prognosis of primary melanoma is presently based on morphological parameters, mainly tumor thickness. However, more reliable prognostic markers are needed that allow a better stratification of patients, especially with regard to therapeutic options. Here, a retrospective study was performed on patients with primary superficial-spreading melanoma (SSM, n=44) or nodular melanoma (n=16) of 1.5–4 mm thickness. Thirty patients had survived the follow-up of 10 years, whereas the other 30 patients developed metastases. Tumor sections were analyzed by immunohistochemistry for the expression of regulators of the cell cycle (p21; retinoblastoma protein (pRb)), of the intrinsic or extrinsic proapoptotic pathways (p53; murine double minute gene 2 protein; tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-R1/DR4; TRAIL-R2/DR5) and of Bcl-2-related proteins (Bcl-2, Mcl-1, Bax, Bak, Bok), which regulate the common mitochondrial apoptotic pathway. In SSM, decrease of Bax and Bak was significantly correlated with a poor prognosis: high Bax was associated with 10-year survival rates of 68%, whereas low Bax resulted in only 26% survival, and high Bak was associated with 10-year survival rates of 62%, whereas low Bak resulted in only 10% survival. Regulators of apoptosis may therefore candidate for independent prognostic markers for primary melanomas. The study underlines the particular role of the mitochondrial apoptosis pathway and of proapoptotic Bcl-2-related proteins for melanoma progression.
Keywords:Apoptosis, Apoptosis Regulatory Proteins, Biological Tumor Markers, Melanoma, Prognosis, Skin Neoplasms, Tertiary Protein Structure, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein
Source:Journal of Investigative Dermatology
Page Range:1366-1371
Date:June 2006
Official Publication:https://doi.org/10.1038/sj.jid.5700192
PubMed:View item in PubMed

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