Strategy for the Incorporation of Tissue Biomarkers in the Clinical Management of

知识上的重大差距阻碍了为子宫内膜患者提供理想的个体化护理 癌症。淋巴清扫的范围和确定哪些患者将从中受益最大 完整的外科分期是尚未解决的临床问题。第二个重要差距是预测能力 哪些低期子宫内膜型子宫内膜癌患者会复发。我们已经使用了 确定子宫内膜癌组织生物标记物的基因组方法。这些生物标志物已经被 在MDACC的一大组子宫内膜癌中得到验证，我们已经记录了它们之间的密切联系 具有分期和复发的特点。接下来，我们将在独立的数据集中验证这些发现。我们假设 在子宫内膜中量化与EMT和雌激素的生长调节作用相关的基因 “生物标记物评分”将提供一个临床上有用的工具，以帮助决定是否进行完全手术。 对诊断为子宫内膜癌的妇女进行分期，并预测哪些妇女处于I期和II期 子宫内膜样癌会复发。在目标1中，我们将验证我们的生物标志物与 子宫内膜癌分期的独立数据集从一系列患者中获得 在梅奥诊所进行了全面的手术分期。我们还将确定计算出的生物标记物得分 从福尔马林固定、石蜡包埋的子宫内膜活检组织来看，这是一个很好的近似分数 根据最后一次子宫切除的组织。我们将确定生物标记物小组与 从梅奥诊所和华盛顿获得的独立数据集中的子宫内膜样癌复发 大学。在目标2中，将使用反相蛋白质裂解物阵列(RPPA)来鉴定蛋白质和 与子宫内膜样癌分期相关的磷酸化蛋白。这些新发现的生物标志物 将被用来增强我们目前现有的面板。我们还将开发执行RPPA的方法 使用福尔马林固定的组织，使这项技术变得与临床样本更相关。终于 RPPA将被用来帮助识别与EIG121相互作用的蛋白质，EIG121是更令人兴奋但最不令人兴奋的蛋白质之一 了解我们现有小组中的生物标记物。

Crucial gaps in knowledge prevent the providing of ideal individualized care to women with endometrial cancer. The extent of lymphadenectomy and the identification of which patients would benefit the most from complete surgical staging are unresolved clinical issues. A second important gap is the ability to predict which women with low stage endometrioid-type endometrial cancer will suffer recurrence. We have used genomic approaches to identify tissue biomarkers of endometrial cancer. These biomarkers have been validated in a large set of endometrial cancers at MDACC, and we have documented their close association with stage and recurrence. Next, we will validate these findings in independent data sets. We hypothesize that quantifying genes associated with EMT and estrogen's growth regulatory actions in the endometrium as a "biomarker score" will provide a clinically useful tool to assist in the decision to perform complete surgical staging on women diagnosed with endometrial cancer and will predict which women with stage I and stage II endometrioid carcinomas will recur. In Aim 1, we will validate the association of our biomarkers with endometrial cancer stage in an independent data set obtained from a series of patients who unden/vent comprehensive surgical staging at the Mayo clinic. We will also establish that the biomarker score computed from formalin-fixed, paraffin-embedded endometrial biopsies is a good approximation of the same scores based on tissue from the final hysterectomy. We will determine the association of the biomarker panel with endometrioid carcinoma recurrence in independent data sets obtained from Mayo Clinic and Washington University. In Aim 2, reverse phase protein lysate array (RPPA) will be used to identify proteins and phospho-proteins that are associated with endometrioid carcinoma stage. These newly identified biomarkers will be used to augment our currently existing panel. We will also develop methodology to perform RPPA using formalin-fixed tissues so that this technology becomes more relevant to clinical samples. Finally RPPA will be used to help identify proteins that interact with EIG121, one of the more exciting but least understood biomarkers in our existing panel.