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）是全球第五大常见恶性肿瘤，是一个主要的国际健康问题。这些肿瘤构成了解剖学上异质性的肿瘤群，产生于不同的解剖位置，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。手术和/或放射治疗和/或化疗等常规治疗与影响言语、吞咽和整体生活质量的显著发病率相关。尽管采取了这些干预措施，但仍有大约50%的患者在局部、区域或远处复发，并伴有高相关死亡率。目前很少有确定的分子标记物可以可靠地用于HNSCC的早期检测或作为预后指标。因此，迫切需要确定预后分子标记物，以便在初始诊断时用于预测患者预后，以便在一开始就使用更合适的治疗方法来改善结果。这个高度合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个不同基因的转录物丰度变化，确定预测肿瘤行为和患者预后的特定分子事件。该项目的具体目的是：1)验证HNSCC临床标本中整体基因表达模式包含可用于预测预后的信息的假设。我们将使用包含28000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)这些实验的综合数据将作为“学习集”来识别与组织病理学、转移、肿瘤和肿瘤相关的基因表达变化和基因组拷贝数畸变。3)我们将使用免疫组织化学技术和市售抗体，利用病理学部和Montefiore医学中心构建的HNSCC组织阵列，评估已鉴定预后基因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