Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center and Chang Gung University College of Medicine, 5 Fushin St., Guishan, Taoyuan, 333, Taiwan.
Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
J Mol Med (Berl). 2021 Jul;99(7):959-966. doi: 10.1007/s00109-021-02064-4. Epub 2021 Mar 25.
Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from one organ to another. However, SEOCs with different histologies are regarded as distinct primary lesions that arise independently from each other. This study was undertaken to compare the mutational landscape of SEOCs with different histologies to confirm or refute the hypothesis of an independent origin. Four patients with synchronous uterine endometrioid carcinoma (UEMC) and ovarian clear cell carcinoma (OCCC) were examined. UEMCs were accompanied by endometrial hyperplasia/endometrioid intraepithelial neoplasia, whereas endometriosis was evident in two cases. Paired UEMC and OCCC specimens were subjected to mutation analysis with massively parallel sequencing. Surprisingly, we found that 50% (2/4) of paired SEOCs with different histologies shared the same somatic mutations, some of which localized in cancer driver genes. Clonality analyses indicated that these tumors were clonally related to each other. Notably, 75% (3/4) of the study patients had Lynch syndrome. The cancer-specific survival figures of patients with synchronous UEMCs and OCCCs were more favorable than those observed in a historical cohort of patients with isolated stage 2/3 OCCCs. Taken together, we set forth a potential explanation that considers clonally related SEOCs as a result of "precursor escape" - whereby precursor cells of endometrial cancer spread beyond the uterus to reach the pelvis and eventually evolve into an OCCC under an increasing mutational burden. KEY MESSAGES: • SEOCs characterized by different histologies are rare. • All cases of SEOCs were accompanied by endometrial hyperplasia. • Fifty percent of SEOCs were clonally related to each other. • Shared mutations in cancer driver genes were evident among SEOCs. • Clonally related SEOCs may be a result of "precursor escape." • Lynch syndrome is highly prevalent in patients with UEMC and synchronous OCCC. • The prognosis of synchronous UEMC and OCCC was favorable.
同步子宫内膜和卵巢癌（SEOC）具有相同的子宫内膜组织学，通常被认为是从一个器官转移到另一个器官的结果。然而，具有不同组织学的 SEOC 被认为是彼此独立发生的不同原发性病变。本研究旨在比较具有不同组织学的 SEOC 的突变景观，以证实或反驳独立起源的假说。对 4 例同步子宫子宫内膜样癌（UEMC）和卵巢透明细胞癌（OCCC）患者进行了检查。UEMC 伴有子宫内膜增生/子宫内膜上皮内瘤变，而在 2 例中可见子宫内膜异位症。对 UEMC 和 OCCC 配对标本进行了大规模平行测序的突变分析。令人惊讶的是，我们发现，具有不同组织学的 50%（2/4）配对 SEOC 共享相同的体细胞突变，其中一些突变定位于癌症驱动基因中。克隆性分析表明，这些肿瘤彼此具有克隆相关性。值得注意的是，75%（3/4）的研究患者患有林奇综合征。同步 UEMC 和 OCCC 患者的癌症特异性生存情况好于孤立性 2/3 期 OCCC 患者的历史队列观察结果。总之，我们提出了一个潜在的解释，认为克隆相关的 SEOC 是“前体逃逸”的结果-即子宫内膜癌的前体细胞扩散到子宫以外的部位到达骨盆，并在不断增加的突变负担下最终演变成 OCCC。关键信息：• 具有不同组织学特征的 SEOC 很少见。• 所有 SEOC 病例均伴有子宫内膜增生。• 50%的 SEOC 彼此具有克隆相关性。• 在 SEOC 中明显存在癌症驱动基因中的共享突变。• 克隆相关的 SEOC 可能是“前体逃逸”的结果。• Lynch 综合征在 UEMC 和同步 OCCC 患者中高发。• 同步 UEMC 和 OCCC 的预后良好。
