Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis
Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis
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DOI：
10.1038/sj.jid.5700192
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发表时间：
2006-06-01
影响因子：
6.5
通讯作者：
Eberle, Juergen
中科院分区：
文献类型：
--
作者：
Fecker, Lothar F.;Geilen, Christoph C.;Eberle, Juergen
原发性黑色素瘤的预后目前是基于形态学参数，主要是肿瘤厚度。然而，需要更可靠的预后标志物，以便更好地对患者进行分层，特别是在治疗选择方面。在此，对原发性浅表扩散性黑色素瘤（SSM，n = 44）或厚度为1.5- 4 mm的结节性黑色素瘤（n = 16）患者进行了一项回顾性研究。30例患者在10年的随访中存活，而其他30例患者发生转移。通过免疫组织化学分析肿瘤切片中细胞周期调节因子的表达（p21;视网膜母细胞瘤蛋白（pRb）），内源性或外源性促凋亡途径（p53;鼠双微小基因2蛋白;肿瘤坏死因子相关凋亡诱导配体（TRAIL）-R1/DR 4; TRAIL-R2/DR 5）和Bcl-2相关蛋白（Bcl-2、Mcl-1、Bax、巴克、博克），它们调节共同的线粒体凋亡途径。在SSM中，Bax和巴克的减少与不良预后显著相关：Bax高与68%的10年生存率相关，而Bax低导致仅26%的生存率，并且巴克高与62%的10年生存率相关，而巴克低导致仅10%的生存率。因此，细胞凋亡调节因子可能是原发性黑色素瘤的独立预后标志物。该研究强调了线粒体凋亡途径和促凋亡Bcl-2相关蛋白在黑色素瘤进展中的特殊作用。
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 1.5-4mm 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.