Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Clin Cancer Res. 2019 Jul 15;25(14):4516-4529. doi: 10.1158/1078-0432.CCR-18-4278. Epub 2019 Apr 22.
Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized.
To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression.
In mixed tumors, gynecologic-type carcinoma components demonstrated lineage-characteristic and lineage-specific alterations, with choriocarcinomatous components sharing some of these as well as demonstrating novel alterations, supporting a clonal relationship with divergent differentiation of the choriocarcinoma from the somatic carcinoma. mutation only occurred in nongestational tumors. Diffuse PD-L1 expression was characteristic of choriocarcinoma in both pure and mixed tumors but not seen in the gynecologic-type carcinoma components.
Given that the somatic carcinomatous and choriocarcinomatous components of mixed tumors have distinct genetic alterations and biomarker expression, separate analysis of these components is required to guide targeted therapy. High PD-L1 expression suggests a role for checkpoint inhibitor-based immunotherapy in tumors with a choriocarcinoma component. The underlying mechanisms by which cancer stem cells reprogram and initiate trophoblastic retrodifferentiation in some somatic tumors warrant further investigation.
绒癌最常见于妊娠（父源或合子来源），但也可能来源于生殖细胞，或作为体细胞肿瘤的一部分发展而来（与患者具有遗传相关性）。后一种类型是侵袭性肿瘤，其潜在的遗传改变尚未得到很好的描述。
为了研究具有绒毛膜癌成分的体细胞肿瘤的不同成分之间的关系、妊娠性和非妊娠性肿瘤之间的遗传差异，并确定潜在的可靶向改变，我们分析了来自 11 个肿瘤的 23 个样本，包括 5 个具有绒毛膜癌分化的妇科型体细胞肿瘤（每个肿瘤有两到三个不同的成分）和 6 个纯绒癌，检测体细胞突变、单核苷酸多态性和 PD-L1 表达。
在混合肿瘤中，妇科型癌成分表现出谱系特征性和谱系特异性改变，绒毛膜癌成分也具有这些改变，并且还具有新的改变，这支持了绒毛膜癌与体细胞癌的克隆关系以及绒毛膜癌从体细胞癌分化的分歧。只有非妊娠性肿瘤中存在 突变。弥漫性 PD-L1 表达是纯和混合肿瘤中绒癌的特征，但在妇科型癌成分中未见。
鉴于混合肿瘤的体细胞癌和绒癌成分具有不同的遗传改变和生物标志物表达，需要对这些成分进行单独分析，以指导靶向治疗。高 PD-L1 表达提示在具有绒癌成分的肿瘤中，检查点抑制剂免疫疗法可能具有作用。一些体细胞肿瘤中癌症干细胞重编程并启动滋养细胞逆行分化的潜在机制值得进一步研究。
