Objective: 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. Methods: 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. Results: （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 (P<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 (P<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 (P<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 (P<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 (P<0.05). Conclusions: 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.
目的： 探讨程序性细胞死亡受体1（PD-1）及其配体（PD-L1）在卵巢上皮性癌（卵巢癌）组织中的表达及其意义。 方法： 选取2002年10月—2013年12月大连医科大学附属第一医院经手术治疗且经病理检查证实为卵巢癌的组织标本180份，包括浆液性癌120份，黏液性癌30份，子宫内膜样癌15份，透明细胞癌15份；从中随机选取50份癌旁的正常卵巢组织标本作为对照。采用免疫组化SP法检测卵巢癌和正常卵巢组织中PD-1及PD-L1的表达，并分析PD-1及PD-L1的表达与卵巢癌患者不同临床病理特征及预后之间的关系。 结果： （1）卵巢癌和正常卵巢组织中PD-1及PD-L1的表达：PD-1表达于癌组织内浸润的淋巴细胞中，PD-L1表达于癌细胞的细胞膜；在癌旁的正常卵巢组织中PD-1及PD-L1均呈阴性表达。卵巢癌、正常卵巢组织中PD-1及PD-L1的阳性表达率分别均为18.3%（33/180）、2.0%（1/50），两者比较，差异有统计学意义（P<0.01）。（2）不同临床病理特征的卵巢癌组织中PD-1及PD-L1的表达：卵巢癌组织中PD-1、PD-L1的阳性表达率，浆液性癌均高于非浆液性癌（包括黏液性癌、子宫内模样癌、透明细胞癌），手术病理分期为Ⅲ、Ⅳ期者高于Ⅰ、Ⅱ期，发病模式为Ⅱ型者高于Ⅰ型，肿瘤累及侧别为双侧卵巢者高于单侧卵巢者，分别比较，差异均有统计学意义（P<0.05）。（3）不同PD-1、PD-L1表达的卵巢癌患者的生存情况：PD-1阳性、阴性表达患者的中位生存时间分别为35、61个月，PD-L1阳性、阴性表达患者的中位生存时间分别为36、61个月，两者分别比较，差异均有统计学意义（P<0.05）。 结论： PD-1及PD-L1在卵巢癌组织中的表达均高于癌旁的正常卵巢组织，特别是浆液性癌较为明显；晚期卵巢癌患者PD-1及PD-L1的表达较高，表明PD-1及PD-L1阳性表达是卵巢癌患者预后不良的指标。.
Keywords: Carcinoma, ovarian epithelial; Immunohistochemistry; Ovarian neoplasms; Programmed cell death 1 receptor.