Tanigawa Masahiko, Naito Yoshiki, Akiba Jun, Kawahara Akihiko, Okabe Yoshinobu, Ishida Yusuke, Ishikawa Hiroto, Hisaka Toru, Fujita Fumihiko, Yasunaga Masafumi, Shigaki Takahiro, Sudo Tomoya, Mihara Yutaro, Nakayama Masamichi, Kondo Reiichiro, Kusano Hironori, Shimamatsu Kazuhide, Okuda Koji, Akagi Yoshito, Yano Hirohisa
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Department of Pathology, Kurume University School of Medicine, Kurume, Japan; Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
Pathol Res Pract. 2018 Dec;214(12):2069-2074. doi: 10.1016/j.prp.2018.10.006. Epub 2018 Oct 19.
We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).
Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%).
PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%).
Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.
我们检测了手术切除的胰腺腺鳞癌(PASC)样本中程序性死亡配体1(PD-L1)的表达。此外,还使用了通过内镜超声引导下细针穿刺活检(EUS-FNA)获取的活检病例评估了检测率。
选取了2009年至2016年间久留米大学医院的15例PASC病例(6例手术切除病例和9例EUS-FNA活检病例)用于评估PD-L1表达。作为对照组,选取了34例胰腺导管腺癌(PDAC)病例。为比较PD-L1的阳性率和强度,使用两种克隆(SP263、E1L3N)进行免疫染色检测。仅将PD-L1的膜表达视为阳性。分别评估了鳞状细胞癌成分(SCc)、腺癌成分(ACc)和免疫细胞中的PD-L1表达。通过计数阳性肿瘤细胞计算PD-L1表达率,并应用肿瘤比例评分(TPS)(TPS;无表达<1%,低表达;1≤TPS≤49%,高表达;≥50%)。
在5例手术切除的PASC样本中观察到PD-L1表达(83%)。这表明在这些病例中SCc呈现高表达。然而,总体TPS显示为低表达。相比之下,PDAC中仅1例(3%)PD-L1呈阳性,TPS显示为低表达。在SP263和E1L3N这两种克隆之间未观察到PD-L1表达的差异。在EUS-FNA样本中,仅1例(11%)发现PD-L1高表达。
尽管使用从EUS-FNA获取的PASC样本的肿瘤细胞进行评估存在困难,但本研究提示PD-L1在PASC的SCc中选择性表达。此外,尽管PD-L1表达较低,但认为免疫检查点抑制剂可对整个TPS范围内的SCc选择性提供治疗效果。