Loss of Proapoptotic Bcl-2-Related Multidomain Proteins in Primary Melanomas Is Associated with Poor Prognosis
| Autor: | Georgi Tchernev, Bachtier M. Kurbanov, Lothar F. Fecker, Jürgen Eberle, Chalid Assaf, Constanze Schwarz, Uwe Trefzer, Christoph C. Geilen, Peter T. Daniel |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pathology medicine.medical_specialty Skin Neoplasms Necrosis Apoptosis Dermatology Nodular melanoma Biochemistry Biomarkers Tumor medicine Humans Melanoma Molecular Biology Gene Aged bcl-2-Associated X Protein biology Retinoblastoma protein Cell Biology Middle Aged Cell cycle Prognosis medicine.disease Protein Structure Tertiary bcl-2 Homologous Antagonist-Killer Protein Cancer research biology.protein Immunohistochemistry Female medicine.symptom Apoptosis Regulatory Proteins |
| Zdroj: | Journal of Investigative Dermatology. 126:1366-1371 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700192 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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