Ju C, Gao J C, Zhang P X, Zhang K N, Yang S, Kang T J, Zhao H Z, Qi W J, Zhang Q P, Kong F D, Guan H W, Shi H
Department of Obstetrics and Gynecology, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
Department of Pathology, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
Zhonghua Fu Chan Ke Za Zhi. 2020 Aug 25;55(8):529-534. doi: 10.3760/cma.j.cn112141-20200301-00155.
To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ,included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. (1) PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC (type Ⅱ) than those of low-grade (type Ⅰ) and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (<0.05). The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.
检测程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1)在上皮性卵巢癌(EOC)组织中的表达,并探讨其表达与临床病理特征及预后的相关性。对2002年10月至2013年12月在大连医科大学附属第一医院接受治疗的180例EOC患者的标本进行病理检查确诊。病理组织标本亚型包括浆液性癌120例、黏液性癌30例、子宫内膜样癌20例、透明细胞癌20例。从180例患者中随机选取50例患者的正常癌旁组织作为对照组。采用免疫组织化学SP法检测上皮性卵巢癌组织中PD-1和PD-L1的表达,并分别分析其表达与临床病理参数及预后的关系。(1)PD-1在浸润于EOC组织的淋巴细胞中表达,PD-L1在癌组织细胞膜上表达。在所有EOC病例中,33例(18.3%,33/180)PD-1和PD-L1均高表达,而对照组仅1例(2.0%,1/50)高表达。两组间差异有统计学意义(<0.01)。(2)在EOC的四种亚型组织标本中,浆液性癌PD-1高表达率为25.0%(30/120),子宫内膜样癌为3/15,黏液性癌为0(0/30),透明细胞癌为0(0/15)。PD-L1高表达率浆液性癌为23.3%(28/120),黏液性癌为3.3%(1/30),子宫内膜样癌为2/15,透明细胞癌为2/15。四种亚型组织标本中PD-1和PD-L1的表达均有显著差异(<0.05)。PD-1和PD-L1均高表达率早期为9.2%(8/87),晚期为26.9%(25/93)。两组间差异有统计学意义(<0.01)。同样,高级别EOC(Ⅱ型)患者中PD-1和PD-L1的表达均显著高于低级别(Ⅰ型)患者,双侧分布的EOC患者中PD-1和PD-L1的表达高于单侧分布患者,差异均有统计学意义(<0.05)。(3)Kaplan-Meier生存分析显示,PD-1和PD-L1均高表达的患者生存时间分别为35个月和36个月,PD-1和PD-L1均低表达的患者生存时间为61个月,差异有统计学意义(<0.05)。EOC组织中PD-1和PD-L1的表达水平高于相邻组织,尤其是浆液性癌。晚期患者标本中PD-1和PD-L1的表达均较高。结果表明,PD-1和PD-L1均高表达是EOC患者预后不良的指标。