Automated quantitative analysis of tissue microarrays reveals an association between high Bcl-2 expression and improved outcome in melanoma
Automated quantitative analysis of tissue microarrays reveals an association between high Bcl-2 expression and improved outcome in melanoma
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DOI：
10.1158/0008-5472.can-04-1387
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发表时间：
2004-12-01
期刊：
影响因子：
11.2
通讯作者：
Kluger, HM
中科院分区：
文献类型：
--
作者：
DiVito, KA;Berger, AJ;Kluger, HM
在转移性黑色素瘤的治疗中加入达卡巴嗪的B细胞淋巴瘤2（Bcl-2）反义基因，与单独使用达卡巴嗪相比，显示出改善的反应率和无进展生存期。对黑色素瘤患者小队列的研究显示Bcl-2表达的变异性（60%-96%阳性）。我们在一个大的患者队列中进行Bcl-2表达的定量分析，以评估与outcome.Tissue微阵列的关联完整的黑色素瘤标本代表402例（339相关的生存数据）进行了分析，我们的AQUA系统进行自动定量分析。自动定量分析使用SIN将像素定义为阵列点内的黑素瘤（肿瘤tumor tmisk），并使用掩模内的Cy 5缀合抗体测量Bel-2表达的强度。生成连续的指数分数，该分数与单位面积的分子数量成正比。评分分为四分位数并与临床变量相关，Bcl-2高表达与整个队列和仅转移性标本的较好结局相关（分别为P = 0.004和P = 0.015）。原发灶的表达高于转移灶（P < 0.0001）。Bcl-2表达与Breslow深度或Clark水平之间无相关性，文献中的不同结果可能是由于使用了小的队列或染色技术的差异。这些结果表明，需要研究来评估Bcl-2表达的定量评估和对Bcl-2靶向治疗的反应之间的关联，以提高对这些药物的反应率。
The addition of B-cell lymphoma 2 (Bcl-2) antisense to dacarbazine in the treatment of metastatic melanoma demonstrates improved response rates and progression-free survival when compared with dacarbazine alone. Studies on small cohorts of melanoma patients have shown variability in Bcl-2 expression (60%-96% positive). We performed quantitative analysis of Bcl-2 expression in a large patient cohort to assess the association with outcome.Tissue microarrays containing intact melanoma specimens representing 402 patients (339 with associated survival data) were analyzed with our AQUA system for automated quantitative analysis. Automated, quantitative analysis uses SIN to define pixels as melanoma (tumor tmisk) within the array spot and measures intensity of Bel-2 expression using a Cy5 conjugated antibody within the mask. A continuous index score is generated, which is directly proportional to the number of molecules per unit area. Scores were divided into quartiles and correlated with clinical variables.High Bcl-2 expression was associated with better outcome in the entire cohort and among metastatic specimens only (P = 0.004 and P = 0.015, respectively). Expression was higher in primary than in metastatic specimens (P < 0.0001). There was no association between Bcl-2 expression and Breslow depth or Clark level.The diverse results within the literature may be due to use of small cohorts or variability in staining technique. These results suggest studies are needed to evaluate the association between quantitative assessment of Bcl-2 expression and response to Bel-2 targeting therapy toward the goal of improved response rates to these drugs.