Loss of MDA-7 expression with progression of melanoma
Loss of MDA-7 expression with progression of melanoma
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DOI：
10.1200/jco.2002.20.4.1069
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发表时间：
2002-02-15
影响因子：
45.3
通讯作者：
Grimm, EA
中科院分区：
文献类型：
--
作者：
Ellerhorst, JA;Prieto, VG;Grimm, EA
目的：黑色素瘤分化相关基因 7 (mda-7) 的异位转移已在体外显示可抑制多种人类肿瘤细胞系的生长并诱导细胞凋亡；正常细胞不会产生类似的效果。因此，mda-7 基因似乎充当一种新型肿瘤抑制因子，并且人们对 mda-7 基因转移作为癌症治疗的潜力感兴趣。本研究的目的是确定 MDA-7 蛋白在原发性黑色素瘤从浅表期到侵袭期以及从局部肿瘤到转移性肿瘤的进展过程中是否丢失。作为次要目标，我们分析了原发性黑色素瘤中的 MDA-7 蛋白表达，以确定其与结果预测因子和生存率的相关性。材料和方法。通过免疫组织化学评估了 41 个原发性黑色素瘤和 41 个转移瘤（包括 24 个配对样本）中的 MDA-7 蛋白表达。对每个样本的阳性细胞百分比和免疫标记的总体强度进行评分。 结果：当将表皮内和浅表浸润部分与原发性肿瘤的深层浸润部分进行比较时，观察到 MDA-7 免疫染色显着降低，反映在数量和强度评分上。将原发性肿瘤与配对转移瘤进行比较时也观察到显着差异。结论：原发性黑色素瘤中MDA-7表达的下调有利于进展至侵袭性和转移性阶段。这些数据支持 Ad-mda7 作为晚期黑色素瘤基因疗法的开发。 (C) 2002 年，美国临床肿瘤学会。
Purpose: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival.Materials and Methods. MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling.Results: Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases.Conclusion: Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma. (C) 2002 by American Society of Clinical Oncology.