Molecular Classification of Primary Cutaneous Melanoma

描述（由申请人提供）：基因表达谱分析有可能彻底改变目前的癌症分类和诊断方法。最近在我们实验室进行的痣，原发性和转移性黑色素瘤的cDNA微阵列分析已经确定了一些基因，其表达水平可用于区分黑色素瘤的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，开发一种新的黑素细胞肿瘤的分子分类。在本申请中，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结果。我们还将评估免疫组化分析的效用，以开发黑色素瘤的分子诊断和预后标志物。我们的目的是：目的1：通过一个大型黑色素瘤患者队列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：探讨免疫组化分析多种分子标记物在原发性黑色素瘤与良性痣鉴别诊断中的应用价值。我们将研究在我们的cDNA微阵列分析中确定的8个标志物的蛋白质表达差异表达的黑色素瘤相比，痣在350原发性黑色素瘤和150痣的测试集，和验证集的75例原发性黑色素瘤中出现的痣。目标3：评估多种分子标记物的免疫组化分析在预测黑色素瘤预后中的作用。我们将研究在我们的cDNA微阵列分析中鉴定为在转移性黑色素瘤中差异表达的8个分子标记物在蛋白质水平分析时是否可以预测黑色素瘤预后。我们将使用免疫组化分析来定量这八个标志物在一组353例原发性黑色素瘤中的表达，这些黑色素瘤具有明确的组织学和随访。总之，这些研究应该更精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.