Yang Xiao, Zhu Guoxing, Yang Zhengjie, Zeng Ke, Liu Fengxiang, Sun Junying
Department of Orthopaedics Surgery, The First Affiliated Hospital of Soochow University, China.
Department of Orthopaedics Surgery, Wuxi No.2 People's Hospital, Nanjing Medical University, China.
Int J Biol Markers. 2018 Nov;33(4):507-513. doi: 10.1177/1724600818774464. Epub 2018 Jun 3.
Chondrosarcoma is a malignancy affecting cartilage and is chemo- and radio-resistant. Novel immune checkpoint inhibitors may play a role in treatment; however, expression of programmed cell death ligand 1/2 (PD-L1/PD-L2) in chondrosarcoma is unreported.
Chondrosarcoma sections were collected and stained immunohistochemically for PD-L1, PD-L2, Ki-67, and TP53. Clinicopathological parameters were collected and analyzed statistically for associations and correlations. PD-L1/PD-L2 positivity was designated using 1% and 5% cutoffs, respectively.
A total of 59 chondrosarcoma samples excised between 1997 and 2017 were collected. There were 40 samples assessed as PD-L1-positive and 25 samples as PD-L2-positive. In univariate analysis, PD-L1 positivity was significantly associated with younger age ( = .001), larger tumor ( = .025), advanced tumor grade ( < .001), and recurrence ( < .001). PD-L1 positivity was not associated with gender, location, serum level of lactate dehydrogenase, or serum level of alkaline phosphatase. PD-L2 positivity was solely significantly associated with younger age ( = .015). The associations were however insignificant in multivariate analysis. PD-L1 expression was significantly correlated with Ki-67 ( < .001) and TP53 ( = .02) expressions. PD-L2 expression was not correlated with either Ki-67 or TP53 expression. When grouped as combined expression (both negative vs. either positive), PD-L1/PD-L2 expression was associated with earlier recurrence ( < .001), and was negatively correlated with expression of Ki-67 ( < .001) but not with the expression of TP53.
PD-L1/PD-L2 is positively expressed in chondrosarcoma and is associated with advanced clinical phenotype. PD-L1/PD-L2 expression is also associated with Ki-67 expression. Our results support the application of immune checkpoint blockade in chondrosarcoma.
软骨肉瘤是一种影响软骨的恶性肿瘤,对化疗和放疗具有抗性。新型免疫检查点抑制剂可能在治疗中发挥作用;然而,软骨肉瘤中程序性细胞死亡配体1/2(PD-L1/PD-L2)的表达情况尚无报道。
收集软骨肉瘤切片,进行PD-L1、PD-L2、Ki-67和TP53的免疫组织化学染色。收集临床病理参数并进行统计学分析,以探讨其关联性和相关性。分别采用1%和5%的临界值来判定PD-L1/PD-L2阳性。
共收集了1997年至2017年间切除的59例软骨肉瘤样本。有40例样本被评估为PD-L1阳性,25例样本为PD-L2阳性。在单因素分析中,PD-L1阳性与较年轻的年龄(P = 0.001)、较大的肿瘤(P = 0.025)、较高的肿瘤分级(P < 0.001)和复发(P < 0.001)显著相关。PD-L1阳性与性别、肿瘤位置、血清乳酸脱氢酶水平或血清碱性磷酸酶水平无关。PD-L2阳性仅与较年轻的年龄显著相关(P = 0.015)。然而,在多因素分析中,这些关联性并不显著。PD-L1表达与Ki-67(P < 0.001)和TP53(P = 0.02)表达显著相关。PD-L2表达与Ki-67或TP53表达均无相关性。当按联合表达分组(两者均为阴性 vs. 任一为阳性)时,PD-L1/PD-L2表达与较早复发相关(P < 0.001),且与Ki-67表达呈负相关(P < 0.001),但与TP53表达无关。
PD-L1/PD-L2在软骨肉瘤中呈阳性表达,并与晚期临床表型相关。PD-L1/PD-L2表达也与Ki-67表达相关。我们的结果支持在软骨肉瘤中应用免疫检查点阻断疗法。