Association between programmed cell death ligand-1 expression and extracranial metastasis in intracranial solitary fibrous tumor/hemangiopericytoma
Association between programmed cell death ligand-1 expression and extracranial metastasis in intracranial solitary fibrous tumor/hemangiopericytoma
复制标题
DOI：
10.1007/s11060-018-2876-7
复制
发表时间：
2018-09-01
影响因子：
3.9
通讯作者：
Sasaki, Hikaru
中科院分区：
文献类型：
--
作者：
Kamamoto, Dai;Ohara, Kentaro;Sasaki, Hikaru
颅内孤立性纤维性肿瘤/血管外皮细胞瘤（SFT/HPC）常表现为颅外转移，治疗选择非常有限。免疫检查点分子尚未在SFT/HPCs中得到很好的研究，它们在颅内SFT/HPCs中的作用尚不清楚。我们采用免疫组化方法研究了16例颅内SFT/HPC患者中程序性细胞死亡-1 （PD-1）、程序性细胞死亡配体-1 （PD-L1）和肿瘤浸润淋巴细胞（TIL）的表达，以确定其与预后是否存在相关性。16例患者中位总生存期（OS）为9.2年，存活患者中位随访期为9.9年。复发13例（81.3%），颅内外转移6例（37.5%）。16例肿瘤均有PD-L1表达，2例肿瘤有PD-1表达。CD3和CD8分别在12例和13例患者的TILs中表达。虽然PD-L1阳性肿瘤细胞的比例与OS、无进展生存期或无转移生存期（MFS）无关，但PD-L1弥漫性染色显示出治疗失败时间（TTF：颅内外转移或死亡时间）缩短的趋势（p = 0.072）。同样，PD-L1的强染色与较短的MFS （p = 0.0084）和TTF （p = 0.033）相关。CD3或CD8的表达与任何预后参数无关。在PD-L1和CD8的联合分析中，弥漫性PD-L1染色合并CD8不表达或稀疏表达与较短的TTF显著相关（p = 0.005），并有缩短MFS的趋势（p = 0.0611）。PD-L1在颅内SFT/HPCs中频繁表达，弥漫性或强烈的PD-L1表达可能与颅外转移的早期发生有关。
Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) often shows extracranial metastasis, and treatment options are very limited. Immune-checkpoint molecules have not been studied well in SFT/HPCs, and their role in intracranial SFT/HPCs remains unclear.We investigated the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TIL) in 16 patients of intracranial SFT/HPC by immunohistochemistry to determine if correlation with prognosis exists.Median overall survival (OS) of 16 patients was 9.2 years, and median follow-up of alive patients was 9.9 years. Recurrence was observed in 13 (81.3%) patients, and extracranial metastasis were observed in 6 (37.5%). PD-L1 expression was observed in all 16 tumors, whereas PD-1 expression was observed in 2. CD3 and CD8 expressions were observed in TILs in 12 and 13 patients respectively. Although the ratio of PD-L1 positive-tumor cells was not associated with OS, progression-free survival, or metastasis-free survival (MFS), diffuse staining of PD-L1 showed a trend toward shorter time to treatment failure (TTF: time to either extracranial metastasis or death) (p = 0.072). Similarly, the intense staining of PD-L1 was associated with shorter MFS (p = 0.0084) and TTF (p = 0.033). CD3 or CD8 expression was not associated with any of the prognostic parameters. In the combined analysis of PD-L1 and CD8, diffuse PD-L1 staining coupled with no or sparse CD8 expression was significantly associated with a shorter TTF (p = 0.005) and showed a trend toward shorter MFS (p = 0.0611).PD-L1 is frequently expressed in intracranial SFT/HPCs, and diffuse or intense PD-L1 expression might be associated with the early occurrence of extracranial metastases.