Department of Gynecology and Obstetrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Republic of Korea.
Pathol Res Pract. 2019 Aug;215(8):152404. doi: 10.1016/j.prp.2019.03.032. Epub 2019 Apr 3.
Brain metastasis from ovarian/peritoneal cancer is a rare disease that has a dismal prognosis. And genomic alterations and immune-profiling in primary ovarian/ peritoneal cancer and brain metastatic tumor tissues have not been fully elucidated. Multiplexed immunofluorescence and whole-exome sequencing of two matched brain metastatic tumor and primary ovarian/peritoneal cancer tissues were performed. The overall density of immune infiltrates in metastatic tissues (brain) was not significantly different from those in primary cancer tissues (case 1 primary: 2.12% and case 1 metastasis: 2.22%; case 2 primary: 1.70%, and case 2 metastasis: 3.46%). Of note, however, PD-L1 expression in the metastases was higher than that in the primary tumors. We found more non-silent mutations, cancer-related genes, loss of heterozygosity (LOH) and longer lengths of copy-number alterations (CNA) in brain metastases compared to primary ovarian/peritoneal cancers. We report immunologic and genomic profiles of primary ovarian/peritoneal cancer with brain metastasis that may not only provide useful information for understanding its pathogenesis, but also clues for further innovative therapeutic treatments for ovarian cancer.
脑转移瘤来源于卵巢/腹膜癌是一种罕见的疾病,预后较差。原发卵巢/腹膜癌和脑转移瘤组织中的基因改变和免疫特征尚未完全阐明。我们对两例配对的脑转移瘤和原发卵巢/腹膜癌组织进行了多重免疫荧光和全外显子测序。转移组织(脑部)中免疫浸润的总体密度与原发癌组织无显著差异(病例 1 原发:2.12%,病例 1 转移:2.22%;病例 2 原发:1.70%,病例 2 转移:3.46%)。然而,值得注意的是,转移瘤中的 PD-L1 表达高于原发瘤。与原发卵巢/腹膜癌相比,我们在脑转移瘤中发现了更多的非同义突变、癌症相关基因、杂合性缺失(LOH)和更长的拷贝数改变(CNA)。我们报告了原发性卵巢/腹膜癌伴脑转移的免疫和基因组特征,这不仅可能为了解其发病机制提供有用的信息,也为卵巢癌的进一步创新治疗提供了线索。