Objective: To investigate the correlation between the expression of programmed death-1(PD-1), PD ligand-1(PD-L1), indoleamine 2, 3-dioxygenase 1(IDO-1) and clinical parameters in sinonasal malignant mucosal melanoma (SNM). Methods: Samples from 86 SNM patients who did not receive immune-targeted therapy and radio-chemotherapy were analyzed for PD-1, PD-L1, and IDO-1 expression by immunohistochemistry. Results: High clinical/pathologic staging, brain metastases and advanced age were independent risk factors of poor prognosis. The overall survival rate of SNM without pigment was lower than that with pigment. PD-1, PD-L1 and IDO-1 expression was not correlated with tumor pigmentation, but correlated with different primary site.PD-1, PD-L1 and IDO-1 were expressed in 47.6% (41/86), 53.5% (46/86) and 58.1% (50/86)of SNM samples respectively. PD-1 was associated with brain metastasis. Negative expression of PD-1(P=0.031) and IDO-1(P=0.017 9) correlated with worse disease-free survival. No significant association was found between PD-L1 and prognosis. For stages Ⅲ, ⅣA and ⅣB patients, PD-1 expression was associated with better outcome (P=0.025), but PD-L1 negative and IDO-1 positive patients hadworse outcome (P>0.05). PD-1 positive and IDO-1 negative stage ⅣC patients had poorer overall survival. Conclusions: In SNM patients, clinical/pathologic staging, brain metastases, age and pigmentation were prognostic indicator. IDO-1 and PD-1 can also be used as reference to evaluate prognosis. Anti-IDO-1 targeted therapy may be suitable for middle to late stage patients, while advanced stage patients might benefit from anti-PD-1 targeted therapy. PD-1/PD-L1 and IDO-1 may be considered as joint targeted therapy.The predictive value of PD-L1 requires further study.
目的： 探讨程序性死亡分子1(PD-1)及其配体(PD-L1)和吲哚胺-2，3-双加氧酶1(IDO-1)在鼻腔鼻窦恶性黑色素瘤(SNM)中的表达及其与患者的临床病理特征和预后的关系。 方法： 采用免疫组织化学的方法对86例未接受放化疗、免疫治疗和分子靶向治疗的SNM样本进行染色，观察PD-1/PD-L1和IDO-1在组织中的表达情况，分析其与临床病理特征及预后的关系。 结果： 临床病理学分期、脑转移、高龄是SNM预后不良的独立危险因素，无色素组SNM总生存率较有色素组低。PD-1/PD-L1和IDO-1的表达与色素统计学无相关性，与SNM累及部位相关。SNM中PD-1/PD-L1和IDO-1的阳性率分别为47.6%(41/86)、53.5%(46/86)和58.1%(50/86)。PD-1的表达与脑转移有关。PD-1阳性和IDO-1阳性患者的无病生存期均较阴性患者长(P＝0.031，P＝0.017 9)。PD-1阳性和IDO-1阳性患者的无病生存期均较阴性患者长。PD-L1的表达与预后无明显相关性。Ⅲ、ⅣA和ⅣB期PD-1阳性的患者预后较好(P＝0.025)，PD-L1阴性和IDO-1阳性患者预后较差(均P>0.05)。ⅣC期PD-1阳性和IDO-1阴性患者总生存率较低(均P<0.05)。 结论： 临床病理学分期、脑转移、年龄和色素可作为预后相关的临床病理学参考指标。PD-1和IDO-1的表达水平可作为评估预后的参考指标。PD-L1在SNM发病及预后判断中的价值有待进一步的研究。.
Keywords: Immunohistochemistry; Melanoma; Molecular targeted therapy; Prognosis.