中文摘要
程序性死亡配体-1(PD-L1)在原发性与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+TIL(肿瘤浸润淋巴细胞)(TILs)和患者生存的相关性。共选取2003年至2018年间收录的212例具有匹配的原发性卵巢和大网膜转移性肿瘤的卵巢HGSC病例进行进一步分析。采用免疫组化方法,我们在全组织切片上评估了CD8+TILs的密度和PD-L1的表达。应用肿瘤比例评分(TPS,截断值1%)和联合阳性评分(CPS,截断值1),PD-L1表达的阳性率相似,但在卵巢和大网膜肿瘤之间存在显著不一致。
使用TPS,PD-L1阳性肿瘤患者的无复发生存期(RFS)和总生存期(OS)显著差于PD-L1阴性肿瘤患者。使用CPS,PD-L1阳性卵巢肿瘤患者的OS显著较差,而RFS未发现显著差异。PD-L1阳性大网膜肿瘤患者的RFS和OS显著较差。在COX多因素分析中,大网膜PD-L1阳性肿瘤(TPS)患者与较差的RFS和OS相关,而卵巢PD-L1阳性肿瘤(TPS)患者与OS相关而非RFS。尽管如此,在单因素和COX多因素分析中,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PD-L1表达与CD8+TILs密度增加相关。通过TPS评估的PD-L1表达与生存的相关性优于CPS,且大网膜肿瘤中PD-L1表达是比卵巢肿瘤更强的预后指标。
展开英文摘要原文
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.
论文信息
- 作者
- Zhang T、Zhou X、Zhang X、Niu S、Chen H、Zhou F
- 第一作者单位
- Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Zhejiang Province, Hangzhou, 310006, China.China
- 通讯作者单位
- Department of Pathology, Zhejiang University School of Medicine Women's Hospital, Zhejiang Province, Hangzhou, 310006, China. fungchew@zju.edu.cn.China
- 期刊
- Virchows Archiv : an international journal of pathology2023 Apr