涎腺腺样囊性癌中PD-L2的表达及临床意义

Expression of PD-L2 in salivary adenoid cystic carcinoma and its clinical significance

目的探讨涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)组织中程序性死亡配体-2(programmed death-ligand 2,PD-L2)的表达及临床意义。方法采用免疫组化EnVision法检测67例SACC中PD-L2的表达,免疫组化双染法检测PD-L2和CD68/CD163共表达情况,并分析PD-L2、CD68、CD163表达与SACC临床病理特征及预后的关系。结果免疫组化结果显示,SACC肿瘤细胞和肿瘤浸润性免疫细胞(tumor-infiltrating immune cell,TIIC)中PD-L2的阳性率分别为17.9%(12/67)、53.7%(36/67)。肿瘤细胞以及TIIC的PD-L2表达均与淋巴结转移相关(P均<0.05),两者在有淋巴结转移组中PD-L2的表达高于无淋巴结转移组;肿瘤细胞以及TIIC中PD-L2的表达均与患者性别、年龄、肿瘤最大径、发病部位、主要结构、临床分期、神经侵犯以及脉管癌栓无关(P均>0.05)。免疫组化双染结果显示,部分TIIC PD-L2阳性细胞表达CD68和CD163;CD68在TIIC PD-L2阴性组与阳性组中的表达差异无显著性(P=0.8791);CD163在TIIC PD-L2阳性组中的表达高于TIIC PD-L2阴性组(P=0.0052)。Kaplan-Meier生存分析显示,肿瘤细胞PD-L2的表达与患者总生存期(overall survival,OS)无关(P=0.4918);TIIC PD-L2阳性患者的OS较阴性患者缩短(P=0.0101);CD68表达与患者OS无关(P=0.0579);而CD163强阳性患者的OS较弱阳性患者缩短(P=0.0291)。TIIC PD-L2阴性+CD68强阳性的SACC患者预后较好(P=0.0393);TIIC PD-L2阳性+CD163强阳性的患者预后最差(P=0.0040)。结论SACC肿瘤细胞以及TIIC PD-L2的表达与淋巴结转移相关。TIIC PD-L2阳性患者的OS较阴性患者缩短。TIIC PD-L2阴性+CD68强阳性的SACC患者预后较好;TIIC PD-L2阳性+CD163强阳性的患者预后最差;这些结果可为SACC的免疫治疗提供实验数据。

Purpose To investigate the expression and clinical significance of programmed death-ligand 2(PD-L2)in salivary adenoid cystic carcinoma(SACC).Methods The expression of PD-L2 in 67 cases of SACC was evaluated by immunohistochemistry,and the co-expression of PD-L2 and CD68/CD163 was detected by double immunohistochemical staining.The relationships between the expression of PD-L2,CD68 and CD163 and the clinicopathological features and prognosis of SACC were also investigated.Results Immunohistochemistry showed that the positive rates of tumor cell(TC)and tumor infiltrating immune cells(TIIC)of PD-L2 in SACC were 17.9%(12/67)and 53.7%(36/67),respectively.PD-L2 expression by TC/TIIC was correlated with lymph node metastasis(P<0.05),and its expression was higher in patients with lymph node metastasis than in patients without lymph node metastasis.There were no significant correlations between TC/TIIC PD-L2 expression and gender,age,tumor diameter,tumor location,tumor structure,clinical stage,nerve invasion and vascular invasion(all P>0.05).Double immunohistochemical staining showed that a portion of TIIC PD-L2 positive cells expressed CD68 and CD163.There was no significant difference in the expression of CD68 between TIIC PD-L2-negative and positive groups(P=0.8791).However,CD163 expression was higher in TIIC PD-L2-positive group than in negative group(P=0.0052).Kaplan-Meier analysis showed that TC PD-L2 expression was not related to the overall survival(OS)(P=0.4918).Patients with positive TIIC PD-L2 expression experienced shortened OS compared with those with negative TIIC PD-L2 expression in SACC(P=0.0101).Based on CD68 expression,there was no difference in OS in SACC(P=0.0579).Patients with high CD163 expression had shortened OS compared with those with low CD163 expression in SACC(P=0.0291).Moreover,our findings showed that patients with negative TIIC PD-L2 expression and high CD68 expression had better outcomes compared with the other groups(P=0.0393).However,patients with positive TIIC PD-L2 expression and high CD163 expression had more unfavourable outcomes compared with the other groups(P=0.0040).Conclusion TC and TIIC PD-L2 expression were correlated with lymph node metastasis.Patients with positive TIIC PD-L2 expression experience shortened OS compared with those with negative TIIC PD-L2 expression in SACC.Patients with negative TIIC PD-L2 expression and high CD68 expression have better outcomes compared with the other groups.Patients with positive TIIC PD-L2 expression and high CD163 expression have more unfavourable outcomes compared with the other groups.The study may provide experimental data for immunotherapy in SACC.