Determining the clinical significance of intraluminal tumor cells in endometrial cancer

项目总结/摘要 子宫内膜癌是美国最常见的妇科恶性肿瘤， 在2010年至2014年期间，每年增加2%，这是少数几种死亡率上升的癌症之一。的 影响子宫内膜癌死亡率的最有力的预后因素是分期，它详细说明了子宫内膜癌的程度， 原发肿瘤已经扩散到子宫外随着时间的推移，分期标准已经演变为新的临床 数据已经出现;然而，一种潜在的重要的传播方式没有纳入子宫内膜癌， 阶段标准是经输卵管扩散，当子宫内膜癌细胞通过子宫内膜脱落时发生。 输卵管进入腹腔。尽管认识到子宫内膜癌细胞具有 细胞分离和经前庭运输的能力，这种机制与其他机制共同发生， 侵袭性肿瘤的特点，我们缺乏经验数据的预后影响经口扩散， 这种关系是否被其他肿瘤特征改变。拟议的《行动纲领》的总体目标 这项研究的目的是确定腔内肿瘤细胞（ILTC）-- 客观衡量经肛门传播和临床结果，并评估是否纳入这一指标 肿瘤特征提高了预测准确性。为了实现我们的目标，我们将从五个大的资源集中起来， 学术医院我们将收集存档的输卵管切片的数字图像并进行病理检查 回顾1,429例子宫内膜癌患者中ILTC的存在情况。这些信息将与 根据现有临床数据确定ILTC与生存结局之间的关系， 组织学亚型和分期（目的1）。我们还将研究ILTC的加入是否改善了预后。 准确性（目标2）。从我们公布的试点数据的结果，我们预计ILTC的存在将与 尤其是在诊断为浆液性肿瘤或I期肿瘤的妇女中。此外，我们预计， 观察一旦阶段被修改以纳入 ILTC状态。这项调查将是第一次对经口传播的影响进行有效分析， 子宫内膜癌预后我们的研究结果具有很高的转化潜力， 改善风险分层，以便更好地指导术后治疗决策， 癌症死亡率

PROJECT SUMMARY/ABSTRACT Mortality from endometrial cancer, the most common gynecologic malignancy in the United States, increased by 2% per year between 2010 and 2014, one of the few cancers to demonstrate rising mortality rates. The most powerful prognostic factor affecting endometrial cancer mortality is stage, which details the extent to which the primary tumor has spread beyond the uterus. Over time, staging criteria have evolved as new clinical data have emerged; however, one potentially important mode of spread not incorporated in endometrial cancer stage criteria is transtubal spread, which occurs when endometrial cancer cells are exfoliated through the fallopian tubes into the abdominal cavity. Despite the recognition that endometrial cancer cells have the capacity for cellular detachment and transtubal transportation, and that this mechanism co-occurs with other aggressive tumor characteristics, we lack empirical data on the prognostic impact of transtubal spread and whether this relationship is modified by other tumor characteristics. The overarching goals of the proposed study are to determine precise estimates of the relationship between intraluminal tumor cells (ILTCs) — an objective measure of transtubal spread — and clinical outcomes, and to assess whether incorporation of this tumor feature improves predictive accuracy. To achieve our goals, we will pool resources from five large academic hospitals. We will collect digital images of archived fallopian tube slides and conduct a pathology review to determine ILTC presence in 1,429 endometrial cancer patients. This information will be merged with existing clinical data to determine the relationship between ILTCs and survival outcomes according to histological subtype and stage (Aim 1). We will also examine whether the addition of ILTCs improves prognostic accuracy (Aim 2). Results from our published pilot data lead us to expect that ILTC presence will be associated with survival, particularly among women diagnosed with serous tumors or stage I tumors. Moreover, we expect to observe greater accuracy in prediction of survival outcomes once stage has been revised to incorporate ILTC status. This investigation will be the first well-powered analysis of the impact of transtubal spread on endometrial cancer prognosis. Our results have high translational potential for refining stage criteria and improving risk stratification, in order to better guide post-operative treatment decisions and reduce endometrial cancer mortality.