Department of Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, End of Keshavarz Ave, Tehran, IR, Iran.
Department of Gynecology Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, IR, Iran.
BMC Cancer. 2022 Dec 29;22(1):1362. doi: 10.1186/s12885-022-10478-7.
Clear cell carcinoma is an uncommon histologic subtype of ovarian and endometrial carcinoma with poor response to Platinium-based chemotherapy agents at high stages. Blockage of Programmed cell Death Ligand-1 (PD-L1), can be used in targeted immunotherapy. This study investigated Mismatch Repair Deficiency (MMR-D) status, PD-L1 expression, and the correlation between PD-L1 expression and microsatellite instability (MSI) status in ovarian and endometrial clear cell carcinomas.
Ovarian clear cell carcinoma (OCCC) (n = 28) and endometrial clear cell carcinoma (ECCC) (n = 28) samples were evaluated for PD-L1 (in tumoral and peri-tumoral inflammatory cells), MSH6 and PMS2 expression by immunohistochemistry (IHC) study. PD-L1 expression > 1% in tumor cells and > 5% in peritumoral inflammatory cells were considered positive.
The prevalence of PD-L1 expression was higher in ECCC (20/28, 71.43%) compared to OCCC tumor cells (16/28, 57.15%) (p > 0.05), while expression in peritumoral inflammatory cells was significantly higher in ECCC (25/28, 89.29%) compared to OCCC (11/28, 39.28%) (p < 0.05). MMR-D was observed in 5 cases, four OCCCs and one ECCC, among which, four (80%) showed PD-L1 expression in peritumoral inflammatory and tumor cells. The only OCCC case with extensive PD-L1 expression in tumor cells (> 50%) exhibited MSH6/MSH2 loss. No significant correlation was noted between PD-L1 expression and the pathologic stage or survival.
PD-L1 expression was significantly associated with clear cell morphology, especially in the endometrium, independent of MMR protein status.
透明细胞癌是卵巢和子宫内膜癌的一种罕见组织学亚型,在晚期对铂类化疗药物反应不佳。阻断程序性细胞死亡配体 1(PD-L1)可用于靶向免疫治疗。本研究调查了卵巢和子宫内膜透明细胞癌中错配修复缺陷(MMR-D)状态、PD-L1 表达以及 PD-L1 表达与微卫星不稳定性(MSI)状态之间的相关性。
评估了 28 例卵巢透明细胞癌(OCCC)和 28 例子宫内膜透明细胞癌(ECCC)样本中 PD-L1(在肿瘤细胞和肿瘤周围炎症细胞中)、MSH6 和 PMS2 的表达情况,采用免疫组织化学(IHC)研究。肿瘤细胞中 PD-L1 表达>1%且肿瘤周围炎症细胞中 PD-L1 表达>5%被认为是阳性。
ECCC 肿瘤细胞中 PD-L1 表达的发生率高于 OCCC(20/28,71.43%)(p>0.05),而肿瘤周围炎症细胞中 PD-L1 表达的发生率显著高于 OCCC(25/28,89.29%)(p<0.05)。5 例(4 例 OCCC 和 1 例 ECCC)存在 MMR-D,其中 4 例(80%)在肿瘤细胞和肿瘤周围炎症细胞中显示 PD-L1 表达。唯一一例肿瘤细胞中 PD-L1 广泛表达(>50%)的 OCCC 病例表现出 MSH6/MSH2 缺失。PD-L1 表达与病理分期或生存无显著相关性。
PD-L1 表达与透明细胞形态显著相关,尤其是在子宫内膜中,与 MMR 蛋白状态无关。