Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine, Kida, Japan.
Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
J Gynecol Oncol. 2022 Sep;33(5):e67. doi: 10.3802/jgo.2022.33.e67.
To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix).
We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated.
MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors.
The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.
为明确日本卵巢癌患者中缺陷错配修复（dMMR）的频率，我们检测了微卫星不稳定性（MSI）状态和免疫组织化学（IHC）亚型，包括子宫内膜样癌（EMC）、透明细胞癌（CCC）或两者的混合（Mix）。
我们登记了 2006 年至 2015 年间在七家参与机构诊断为 EMC/CCC/Mix 的 390 名患者。对中央病理审查委员会确认符合条件的 339 名患者进行了 MSI、IHC 和 MutL 同源物 1 甲基化分析。对具有林奇综合征（LS）相关癌症病史（如结直肠癌和子宫内膜癌）的患者的组织也进行了调查。
2/217 例 CCC（0.9%）、10/115 例 EMC（8.7%）和 1/4 例 Mix（25%）存在 MSI-H 状态。此外，5/219 例（2.3%）、16/115 例（14.0%）和 1/4 例（25%）的 CCC、EMC 和 Mix 患者存在 MMR 蛋白表达缺失（LoE-MMR）。EMC 中 MSI-H 和 LoE-MMR 的发生率显著更高（p<0.001）。有 MMR 表达和 LoE-MMR 的患者的中位（范围）年龄分别为 54（30-90）和 46（22-76）（p=0.002）。在多变量分析中，晚期和组织学类型被确定为预后因素。
EMC/CCC 的 dMMR 率与西方国家报道的相似。在日本，由于 CCC 的比例增加，dMMR 频率较高。
