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首页> 外文期刊>Gynecologic Oncology: An International Journal >Does the primary site really matter? Profiling mucinous ovarian cancers of uncertain primary origin (MO-CUP) to personalise treatment and inform the design of clinical trials
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Does the primary site really matter? Profiling mucinous ovarian cancers of uncertain primary origin (MO-CUP) to personalise treatment and inform the design of clinical trials

机译：主要网站是否真的很重要？ 剖析不确定的主要原产地（Mo-Cup）的粘液卵巢癌以个性化治疗，并告知临床试验的设计

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摘要

ObjectiveAdvanced stage mucinous ovarian cancers are diagnostically and therapeutically challenging. Histotype specific trials have failed due to low recruitment after excluding non-ovarian primaries. Mucinous ovarian cancers are commonly metastatic from other sites however lack definitive diagnostic markers. We suggest a classification of mucinous ovarian cancers of uncertain primary origin ‘MO-CUPs’ in clinical trials. This study aims to identify drug targets to guide treatment and future trials. MethodsWe analyzed a large de-identified, multi-platform tumor profiling dataset of MO-CUPs enriched for advanced stage and recurrent cases submitted to Caris Life Sciences. Available data included a 45-gene next-generation sequencing (NGS) panel, gene amplification ofHER2andcMETand 18 immunohistochemical (IHC) markers of drug sensitivity/resistance. ResultsMucinous tumors from 333 patients were analyzed, including 38 borderline tumors and 295 invasive cancers. The most common mutations in a subset (n?=?128) of invasive cancers wereKRAS(60%),TP53(38%),PIK3CA(13%) andPTEN(9%). Borderline tumors had higher rates ofBRAFmutations, andPGPandTOP2Aoverexpression than invasive cases.KRASmutant invasive cancers had lower expression of thymidylate synthase (p?=?0.01) and higher expression ofTUBB3(p?=?0.01) thanKRASwildtype tumors. ConclusionsTo our knowledge, this is the largest series profiling mucinous ovarian cancers and almost certainly includes cases of ovarian and non-ovarian origin. Given the difficulty recruiting patients to histotype-specific trials in rare subsets of ovarian cancer, it may be more important to focus on identifying potential treatment targets and to personalise treatment and design clinical trials in MO-CUPS agnostic of primary site to overcome these issues.
机译：特视演阶段粘液卵巢癌是诊断和治疗上的挑战性。组织型特定试验由于低卵巢初级初级招生而失败。粘液卵巢癌是来自其他网站的常规转移，但缺乏明确的诊断标志物。我们建议在临床试验中对不确定的主要原产地'Mo-Cums'粘液卵巢癌的分类。本研究旨在识别指导治疗和未来试验的药物目标。方法分析了大量的DE识别的多平台肿瘤分析数据集，富集的MO-CUPS富集，致力于提交给Caris Life Sciences的经常性案例。可用数据包括一个45-基因下一代测序（NGS）面板，基因扩增ANDER2ANDCMETAND 18免疫组化（IHC）药物敏感性/抗性的标记。分析来自333名患者的结果糊状肿瘤，包括38个边界肿瘤和295例侵袭性癌症。侵入性癌症（n？=β128）中最常见的突变（60％），TP53（38％），Pik3Ca（13％）和僵酮（9％）。边缘肿瘤患者具有较高的Brafurations，AndpGPandtop2aoverexpression，而不是侵入性情况。俗霉素侵袭性癌症具有较低的胸苷合酶（p≤X.01）表达，尚表达Δb3（p？= 0.01）谢天谢。结论我们的知识，这是最大的血杂体卵巢癌，几乎肯定包括卵巢和非卵巢起源的案例。鉴于患者难以募集卵巢癌稀有子集中的组型特异性试验，专注于确定潜在治疗目标和个性化莫杯中的治疗和设计临床试验可能更为重要，以克服这些问题。

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