Zhang Tao, Zhou Xin, Zhang Xiaofei, Niu Shuang, Chen Hao, Zhou Feng
Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Zhejiang Province, Hangzhou, 310006, China.
Department of Pathology, Zhejiang University School of Medicine Women's Hospital, Zhejiang Province, Hangzhou, 310006, China.
Virchows Arch. 2023 Apr;482(4):755-766. doi: 10.1007/s00428-023-03512-x. Epub 2023 Feb 21.
Differential expression of programmed death-1 ligand (PD-L1) and its clinical significance in primary and metastatic ovarian high-grade serous carcinoma (HGSC) have not been defined. Thus, we investigated the PD-L1 expression of paired ovarian primary and omental metastatic HGSC and its correlation with CD8 + tumor-infiltrating lymphocyte (TILs) and patient survival. A total of 212 cases of ovarian HGSCs with matched primary ovarian and metastatic omental tumors accessioned between 2003 and 2018 were selected for further analysis. Using immunohistochemistry, we evaluated the density of CD8 + TILs and expression of PD-L1 on whole tissue sections. Applying tumor proportion score (TPS, cutoff 1%) and combined positive score (CPS, cutoff 1), the prevalence of PD-L1 expression was similar but with significant discordance in ovarian and omental tumor. Using TPS, patients with PD-L1-positive tumors demonstrated significantly worse recurrence free survival (RFS) and overall survival (OS) than patients with PD-L1-negative tumors. Using CPS, patients with PD-L1-positive ovarian tumors demonstrated significantly worse OS while no significant difference in RFS was found. Patients with PD-L1-positive omental tumors demonstrated significantly worse RFS and OS. Patients with omental PD-L1-positive tumors (TPS) were associated with poorer RFS and OS, while patients with ovarian PD-L1-positive tumors (TPS) were associated with OS not RFS, in COX multivariant analysis. Nonetheless, ovarian and omental high CD8 TILs density was not associated with worse OS in univariant and COX multivariant analysis. PD-L1 expression in ovarian and omental tumor associated with an increased CD8 + TILs density. PD-L1 expression by TPS was better correlated with survival than by CPS, and PD-L1 expression in omental tumors was a stronger prognostic indicator than that in ovarian tumors.
程序性死亡-1配体(PD-L1)在原发性和转移性卵巢高级别浆液性癌(HGSC)中的差异表达及其临床意义尚未明确。因此,我们研究了配对的卵巢原发性和大网膜转移性HGSC中PD-L1的表达及其与CD8 +肿瘤浸润淋巴细胞(TILs)和患者生存率的相关性。选取了2003年至2018年间登记的212例具有匹配的原发性卵巢和转移性大网膜肿瘤的卵巢HGSC病例进行进一步分析。我们采用免疫组织化学方法,评估了全组织切片上CD8 + TILs的密度和PD-L1的表达。应用肿瘤比例评分(TPS,临界值1%)和联合阳性评分(CPS,临界值1),PD-L1表达的患病率相似,但在卵巢和大网膜肿瘤中存在显著不一致。使用TPS时,PD-L1阳性肿瘤患者的无复发生存期(RFS)和总生存期(OS)明显比PD-L1阴性肿瘤患者差。使用CPS时,PD-L1阳性卵巢肿瘤患者的OS明显较差,而在RFS方面未发现显著差异。PD-L1阳性大网膜肿瘤患者的RFS和OS明显较差。在COX多变量分析中,大网膜PD-L1阳性肿瘤(TPS)患者的RFS和OS较差,而卵巢PD-L1阳性肿瘤(TPS)患者的OS较差而非RFS。然而,在单变量和COX多变量分析中,卵巢和大网膜高CD8 TILs密度与较差的OS无关。卵巢和大网膜肿瘤中的PD-L1表达与CD8 + TILs密度增加相关。TPS法检测的PD-L1表达与生存率的相关性优于CPS法,大网膜肿瘤中的PD-L1表达比卵巢肿瘤中的更强的预后指标。