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