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程序性细胞死亡配体-1 表达与颅内孤立性纤维肿瘤/血管外皮细胞瘤颅外转移的相关性。

Association between programmed cell death ligand-1 expression and extracranial metastasis in intracranial solitary fibrous tumor/hemangiopericytoma.

机构信息

Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

出版信息

J Neurooncol. 2018 Sep;139(2):251-259. doi: 10.1007/s11060-018-2876-7. Epub 2018 Apr 19.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

颅内孤立性纤维瘤/血管外皮细胞瘤(SFT/HPC)常发生颅外转移,治疗选择非常有限。免疫检查点分子在 SFT/HPC 中的研究还不够充分,其在颅内 SFT/HPC 中的作用尚不清楚。

方法

我们通过免疫组化检测了 16 例颅内 SFT/HPC 患者中程序性细胞死亡蛋白-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。

结果

16 例患者的中位总生存期(OS)为 9.2 年,存活患者的中位随访时间为 9.9 年。13 例(81.3%)患者复发,6 例(37.5%)患者发生颅外转移。所有 16 例肿瘤均有 PD-L1 表达,而 PD-1 表达仅见于 2 例。CD3 和 CD8 在 TIL 中的表达分别见于 12 例和 13 例患者。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 的弥漫性染色提示治疗失败时间(TTF:出现颅外转移或死亡的时间)更短(p=0.072)。同样,PD-L1 的强烈染色与较短的 MFS(p=0.0084)和 TTF(p=0.033)相关。CD3 或 CD8 的表达与任何预后参数均无关。在 PD-L1 和 CD8 的联合分析中,弥漫性 PD-L1 染色伴有无或稀疏 CD8 表达与较短的 TTF 显著相关(p=0.005),并显示出较短的 MFS 趋势(p=0.0611)。

结论

PD-L1 在颅内 SFT/HPC 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。

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