Molecular Classification of Primary Cutaneous Melanoma

描述(由申请人提供)：基因表达谱有可能彻底改变目前癌症分类和诊断的方法。最近，我们实验室对葡萄胎、原发和转移性黑色素瘤进行了基因芯片分析，发现了一些基因的表达水平，这些基因的表达水平可以用来区分黑色素瘤肿瘤进展级联过程中的已知标志。这些研究表明，基因表达谱可用于开发一种新的黑素细胞肿瘤的分子分类。在这个应用中，我们建议通过使用基因表达谱来开发黑色素瘤的分子分类来扩展这些观察。我们还将评估免疫组织化学分析在开发黑色素瘤分子诊断和预后标记物方面的作用。我们的目标是：目标1：通过对大量黑色素瘤患者的基因表达谱分析，对原发性黑色素瘤分子亚型进行分类。目的：评价免疫组织化学多分子标志物分析在鉴别原发性黑色素瘤和良性黑色素瘤中的价值。我们将检测在我们的基因芯片分析中识别的八种标记在黑色素瘤中差异表达的蛋白质表达，并与350例原发性黑色素瘤和150例色素痣的测试组以及75例发生于痣的原发性黑色素瘤的验证组进行比较。目的：评价免疫组织化学分析多分子标志物在预测黑色素瘤预后中的作用。我们将检验在我们的cDNA微阵列分析中发现的在转移性黑色素瘤中差异表达的八个分子标记在蛋白质水平上是否可以预测黑色素瘤的预后。我们将使用免疫组织化学分析来量化这八种标记物在353例有明确组织学特征的原发性黑色素瘤队列中的表达，并进行随访。总体而言，这些研究应该更准确地描述黑色素瘤异质性的分子基础，并确定新的诊断和预后标记物。

DESCRIPTION (provided by applicant): Gene expression profiling has the potential to revolutionize current approaches to cancer classification and diagnosis. Recent cDNA microarray analyses of moles, primary and metastatic melanomas performed in our laboratory have identified a number of genes whose expression level can be used to distinguish between known landmarks in the tumor progression cascade of melanoma. These studies have suggested the utility of gene expression profiling to develop a novel molecular classification of melanocytic neoplasms. In this application, we propose to extend these observations by developing a molecular classification of melanoma using gene expression profiling. We will also assess the utility of immunohistochemical analysis to develop molecular diagnostic and prognostic markers for melanoma. Our aims are: Aim 1: To classify the molecular subtypes of primary melanoma by gene expression profiling of a large cohort of melanoma patients. Aim 2: To assess the utility of immunohistochemical analysis of multiple molecular markers to differentiate primary melanomas from benign nevi. We will examine the protein expression of eight markers identified in our cDNA microarray analysis as being differentially expressed in melanomas when compared with nevi in a test set of 350 primary melanomas and 150 nevi, and a validation set of 75 cases of primary melanoma arising in a nevus. Aim 3: To assess the utility of immunohistochemical analysis of multiple molecular markers for their ability to predict the prognosis associated with melanoma. We will examine whether eight molecular markers identified in our cDNA microarray analysis as being differentially expressed in metastatic melanomas can predict melanoma prognosis when analyzed at the protein level. We will use immunohistochemical analysis to quantitate expression of these eight markers in a cohort of 353 primary melanomas with defined histology and follow up. Overall, these studies should more precisely characterize the molecular basis of melanoma heterogeneity, and identify novel diagnostic and prognostic markers for primary melanoma.