CLINICAL CORRELATIVE STUDIES IN GERM CELL TUMORS

生殖细胞肿瘤(GCT)是一种可治愈的恶性肿瘤，医生 必须区分好的风险和差的风险属性，并选择 为风险较高或风险较低的患者设计的治疗方案。 尽管好的和差的风险类别的几个分配标准 现有的，目前可用的模型基于患者的预处理 临床特征不准确。约10%的良好风险 患者仍然死亡，约三分之一的贫困风险患者幸存下来。 尽管预后指标不佳，但仍接受标准治疗。近期 我们机构大量生成的数据表明，一个或多个 更多的肿瘤标志物可能是更好的，或更多的预后 指标。这项建议的具体目标是涉及四个方面 肿瘤反应和患者生存的假定预后标志物： (1)甲胎蛋白(AFP)和/或的清除率(半衰期) 人绒毛膜促性腺激素(HCG)在化疗后的变化 使用每周标记分析；(2)初选中的12P拷贝数 12P涂抹探针确定肿瘤；(3)TP53在人卵巢癌组织中的表达 (4)Hst1/kFGF在原发肿瘤中的表达。这个 具体假设是甲胎蛋白的半衰期延长 和/或hCG、高12P拷贝数、突变型tp53突变和hst-L/kFGF型 表达是预后较差的发现，可能是独立的。 预测预后的因素。来自纪念医院和 西南肿瘤组与纪念馆贫困高危患者 医院将被计入特定于 风险状态。每周一次的甲胎蛋白和人绒毛膜促性腺激素检测将在 开始化疗以确定标记物的半衰期清除。 将获得原发肿瘤并研究12P拷贝数， 突变型TP53的表达和HST-1/kFGF的表达。生物统计学 将使用Logistic和COX回归技术进行分析 要确定这四个变量中每个变量的重要性， 存在标准的预后变量。如果其中一个或多个 四个新变量独立预测治疗结果和患者 生存，那么一个更好的算法来选择治疗 患者的个体化可以发展。

Germ Cell Tumors (GCT) are a curable malignancy in which the physician must discriminate between good risk and poor risk attributes and choose a treatment program designed for good risk or poor risk patients. Although several allocation criteria for good and poor risk categories exist, the currently available models based on a patient's pretreatment clinical characteristics are imprecise. About 10% of good risk patients still die, and about one-third of poor risk patients survive with standard treatment despite poor prognostic indicators. Recent data largely generated at our institution suggest that one or more additional tumor markers may be better, or additional, prognostic indicators. The Specific Aims of this proposal are to relate four putative markers of prognosis to tumor response and patient survival: (1) the rate of clearance (half-life) of alphafetoprotein (AFP) and/or human chorionic gonadotropin (HCG) after initiation of chemotherapy using weekly marker assays; (2) the 12p copy number in the primary tumor determined by 12p painting probes; (3) TP53 expression in the primary tumor; and (4) Hst1/kFGF expression in primary tumors. The specific hypotheses are that a prolonged half-life clearance of AFP and/or HCG, high 12p copy number, mutant TP53 mutation, and Hst-l/kFGF expression are poor prognostic findings which may be independent predictors of prognosis. Good risk patients from Memorial Hospital and the Southwest Oncology Group and poor risk patients from Memorial Hospital will be accrued onto prospective clinical trials specific to risk status. Weekly assays of AFP and HCG will be obtained after the initiation of chemotherapy to determine the marker half-life clearance. Primary tumors will be obtained and studied for 12p copy number, mutant TP53 expression, and Hst-1/kFGF expression. Biostatistical analyses will be performed using logistic and Cox regression techniques to determine the significance of each of these four variables in the presence of standard prognostic variables. If one or more of these four new variables independently predicts treatment outcome and patient survival, then a better algorithm for the selection of treatment for the individual patient can be developed.