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的癌症分类和诊断方法。最近，我们实验室对痣、原发性和转移性黑色素瘤进行了cDNA微阵列分析，发现了一些基因，其表达水平可用于区分黑色素瘤肿瘤进展级联中的已知标志。这些研究表明，基因表达谱的效用，以发展一种新的分子分类黑色素细胞肿瘤。在这个应用中，我们建议通过使用基因表达谱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黑色素瘤分子诊断和预后标志物开发中的应用。我们的目标是：目的1：通过大量黑色素瘤患者的基因表达谱对原发性黑色素瘤的分子亚型进行分类。目的2：评估多种分子标记的免疫组织化学分析在区分原发性黑色素瘤和良性痣中的应用。我们将在350例原发性黑色素瘤和150例痣的测试集和75例原发性黑色素瘤的验证集中，检测在我们的cDNA微阵列分析中鉴定出的8个标记物的蛋白质表达，这些标记物在黑色素瘤中与痣中的差异表达。目的3：评估多种分子标记物免疫组织化学分析在预测黑色素瘤预后方面的效用。我们将研究在我们的cDNA微阵列分析中鉴定出的在转移性黑色素瘤中差异表达的8个分子标记是否可以在蛋白质水平上预测黑色素瘤的预后。我们将使用免疫组织化学分析在353例具有明确组织学和随访的原发性黑色素瘤队列中定量测定这8种标记物的表达。总的来说，这些研究应该更准确地描述黑色素瘤异质性的分子基础，并确定原发性黑色素瘤的新诊断和预后标志物。

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.