Array-based outcome prediction in head and neck cancer

描述(申请人提供)：头颈部鳞状细胞癌(HNSCC)是全球第五大最常见的恶性肿瘤，是一个主要的国际健康问题。这些肿瘤构成了一个解剖异质性的肿瘤组，起源于不同的解剖位置，包括口腔、口咽、下咽、喉和鼻咽。HNSCC的治疗计划在很大程度上取决于疾病出现时的解剖分期。传统的手术和/或放射治疗和/或化疗与严重的发病率有关，影响言语、吞咽和整体生活质量。尽管采取了这些干预措施，但约50%的患者在当地、地区性或遥远的地点观察到疾病复发，相关死亡率很高。几乎没有已确定的分子标志物可以可靠地用于HNSCC的早期检测或作为预后指标。因此，迫切需要确定可在最初诊断时用于预测患者预后的预后分子标记物，以便在开始时使用更合适的治疗方法来改善预后。这项高度协作的研究项目的目标是通过测量100个独立肿瘤样本中至少20,000个不同基因的转录丰度变化，确定预测这种疾病中肿瘤行为和患者结局的特定分子事件。该项目的具体目标是：1)检验假设，即HNSCC临床标本中的全球基因表达模式包含可用于预测预后的信息。我们将使用包含28,000个cdna克隆的人类cDNA微阵列对100例HNSCC患者的肿瘤样本进行cDNA表达阵列分析和比较基因组杂交(CGH)阵列分析；2)这些实验的组合数据将被用作“学习集”，以确定与这些患者的组织病理学、转移、临床结果和生存相关的基因表达变化和基因组拷贝数异常3)我们将使用免疫组织化学技术和商用抗体，使用病理科和蒙菲奥里医学中心建立的HNSCC组织阵列，评估已确定的预后基因的产物的数量和细胞分布

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, representing a major international health problem. These tumors constitute an anatomically heterogenous group of neoplasms, arising from diverse anatomic locations including the oral cavity, oropharynx, hypopharynx, larynx and nasopharynx. Treatment planning for HNSCC depends largely on anatomical staging of the disease at presentation. Conventional treatment with surgery and/or radiation therapy, and/or chemotherapy is associated with significant morbidity affecting speech, swallowing and overall quality of life. Despite these interventions, recurrence of the disease is observed in about 50% of patients, locally, regionally or at a distant site with high rates of associated mortality. There have been few identified molecular markers that can be reliably used in early detection of HNSCC or as indicators of prognosis. There is therefore an urgent need to identify prognostic molecular markers that can be used at the time of initial diagnosis to predict patient prognosis so that more appropriate treatments can be used at the outset to improve outcome. The goal of this highly collaborative research project is to identify the specific molecular events that predict tumor behavior and patient outcome in this disease by measuring variation in transcript abundance for at least 20,000 different genes in one hundred independent tumor samples. The specific aims of the project are: 1) To test the hypothesis that the pattern of global gene expression in a HNSCC clinical specimen contains information that can be used as a predictor of prognosis. We will apply cDNA expression array analysis and comparative genome hybridization (CGH) array analysis to a set of 100 HNSCC patient tumor samples using a human cDNA microarray containing 28,000 cDNA clones, 2) Combined data from these experiments will be used as a "learning set" to identify gene expression changes and genome copy number aberrations that correlate with histopathology, metastasis, clinical outcome and survival in these patients 3) We will assess the quantity and cellular distribution of the products of identified prognostic genes using immunohistochemical techniques with commercially available antibodies using a HNSCC tissue array constructed in the Department of Pathology and Montefiore Medical Center